Frans S. S. Leijten

High-Frequency Oscillations as a New Biomarker in Epilepsy

The discovery that electroencephalography (EEG) contains useful information at frequencies above the traditional 80Hz limit has had a profound impact on our understanding of brain function. In epilepsy, high‐frequency oscillations (HFOs, >80Hz) have proven particularly important and useful. This literature review describes the morphology, clinical meaning, and pathophysiology of epileptic HFOs. To record HFOs, the intracranial EEG needs to be sampled at least at 2,000Hz. The oscillatory events can be visualized by applying a high‐pass filter and increasing the time and amplitude scales, or EEG time‐frequency maps can show the amount of high‐frequency activity. HFOs appear excellent markers for the epileptogenic zone. In patients with focal epilepsy who can benefit from surgery, invasive EEG is often required to identify the epileptic cortex, but current information is sometimes inadequate. Removal of brain tissue generating HFOs has been related to better postsurgical outcome than removing the seizure onset zone, indicating that HFOs may mark cortex that needs to be removed to achieve seizure control. The pathophysiology of epileptic HFOs is challenging, probably involving populations of neurons firing asynchronously. They differ from physiological HFOs in not being paced by rhythmic inhibitory activity and in their possible origin from population spikes. Their link to the epileptogenic zone argues that their study will teach us much about the pathophysiology of epileptogenesis and ictogenesis. HFOs show promise for improving surgical outcome and accelerating intracranial EEG investigations. Their potential needs to be assessed by future research. Ann Neurol 2012;71:169–178

Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator

BackgroundAcute axonal polyneuropathy has been found in patients with multiple organ dysfunction syndrome. This ‘critical illness polyneuropathy’ (CIP) has been associated with difficult weaning from the ventilator in retrospective studies.ObjectiveTo test the hypothesis that CIP is related to the degree and number of organ dysfunctions, and to weaning problems.DesignProspective study of 18 months.SettingA multidisciplinary intensive care unit in a general hospital.SubjectsThirty-eight patients under 75 years of age who had been mechanically ventialted for more than 7 days, without previous signs of or risk factors for polyneuropathy.MeasuresOrgan dysfunctions were quantified using a dynamic scoring system (0–12 points). Electromyography studies were performed during mechanical ventilation to identify patients with and without CIP.ResultsCIP was present in 18 out of 38 patients and associated with an increased organ dysfunction score (5.3±1.8 vs. 3.6±1.5;p=0.003) and number of organs involved [median (range): 4 (3–5) vs. 2 (1–4);p=0.009], in particular cardiovascular (p=0.003), renal (p=0.04), and hematopoietic failure (p=0.04). Patients with polyneuropathy were ventilated longer, but this was not clearly due to more difficult weaning [median: 16.5 (1–48) vs. 9.5 (1–38) days;p=0.26]. Polyneuropathy was present in 2 of 4 patients with normal weaning.ConclusionsAxonal polyneuropathy is related to the severity of multiple-organ-dysfunction syndrome. Its presence does not necessarily implicate difficult weaning from artificial ventilation.

Measurement of the Conductivity of Skull, Temporarily Removed During Epilepsy Surgery

The conductivity of the human skull plays an important role in source localization of brain activity, because it is low as compared to other tissues in the head. The value usually taken for the conductivity of skull is questionable. In a carefully chosen procedure, in which sterility, a stable temperature, and relative humidity were guaranteed, we measured the (lumped, homogeneous) conductivity of the skull in five patients undergoing epilepsy surgery, using an extended four-point method. Twenty-eight current configurations were used, in each of which the potential due to an applied current was measured. A finite difference model, incorporating the geometry of the skull and the electrode locations, derived from CT data, was used to mimic the measurements. The conductivity values found were ranging from 32 mS/m to 80 mS/m, which is much higher than the values reported in other studies. Causes for these higher conductivity values are discussed.

Neurophysiologic correlates of fMRI in human motor cortex.

The neurophysiological underpinnings of functional magnetic resonance imaging (fMRI) are not well understood. To understand the relationship between the fMRI blood oxygen level dependent (BOLD) signal and neurophysiology across large areas of cortex, we compared task related BOLD change during simple finger movement to brain surface electric potentials measured on a similar spatial scale using electrocorticography (ECoG). We found that spectral power increases in high frequencies (65–95 Hz), which have been related to local neuronal activity, colocalized with spatially focal BOLD peaks on primary sensorimotor areas. Independent of high frequencies, decreases in low frequency rhythms (<30 Hz), thought to reflect an aspect of cortical‐subcortical interaction, colocalized with weaker BOLD signal increase. A spatial regression analysis showed that there was a direct correlation between the amplitude of the task induced BOLD change on different areas of primary sensorimotor cortex and the amplitude of the high frequency change. Low frequency change explained an additional, different part of the spatial BOLD variance. Together, these spectral power changes explained a significant 36% of the spatial variance in the BOLD signal change (R2 = 0.36). These results suggest that BOLD signal change is largely induced by two separate neurophysiological mechanisms, one being spatially focal neuronal processing and the other spatially distributed low frequency rhythms. Hum Brain Mapp, 2011.

Electrocorticographic discharge patterns in glioneuronal tumors and focal cortical dysplasia.

Summary:  Purpose: To determine whether highly epileptiform electrocorticographical discharge patterns occur in patients with glioneuronal tumors (GNTs) and focal cortical dysplasia (FCD) and whether specific histopathological features are related to such patterns.

Critical illness polyneuropathy A review of the literature, definition and pathophysiology

We present a review of the clinical characteristics, and electromyographical and pathological findings of critical illness polyneuropathy by a comparison of ten studies, leading to a definition. Controversies about the nature of CIP, the interpretation of neurophysiological and pathological findings, and differential diagnoses are discussed.

Brain–computer interfacing based on cognitive control

Brain–computer interfaces (BCIs) translate deliberate intentions and associated changes in brain activity into action, thereby offering patients with severe paralysis an alternative means of communication with and control over their environment. Such systems are not available yet, partly due to the high performance standard that is required. A major challenge in the development of implantable BCIs is to identify cortical regions and related functions that an individual can reliably and consciously manipulate. Research predominantly focuses on the sensorimotor cortex, which can be activated by imagining motor actions. However, because this region may not provide an optimal solution to all patients, other neuronal networks need to be examined. Therefore, we investigated whether the cognitive control network can be used for BCI purposes. We also determined the feasibility of using functional magnetic resonance imaging (fMRI) for noninvasive localization of the cognitive control network.

The Added Value of [18F]-Fluoro-D-deoxyglucose Positron Emission Tomography in Screening for Temporal Lobe Epilepsy Surgery

Purpose:[18F]‐Fluoro‐d‐deoxyglucose positron emission tomography (FDG‐PET) is an expensive, invasive, and not widely available technique used in the presurgical evaluation of temporal lobe epilepsy. We assessed its added value to the decision‐making process in relation to other commonly used tests.

Time–frequency analysis of single pulse electrical stimulation to assist delineation of epileptogenic cortex

Epilepsy surgery depends on reliable pre-surgical markers of epileptogenic tissue. The current gold standard is the seizure onset zone in ictal, i.e. chronic, electrocorticography recordings. Single pulse electrical stimulation can evoke epileptic, spike-like responses in areas of seizure onset also recorded by electrocorticography. Recently, spontaneous pathological high-frequency oscillations (80-520 Hz) have been observed in the electrocorticogram that are related to epileptic spikes, but seem more specific for epileptogenic cortex. We wanted to see whether a quantitative electroencephalography analysis using time-frequency information including the higher frequency range could be applied to evoked responses by single pulse electrical stimulation, to enhance its specificity and clinical use. Electrocorticography data were recorded at a 2048-Hz sampling rate from 13 patients. Single pulse electrical stimulation (10 stimuli, 1 ms, 8 mA, 0.2 Hz) was performed stimulating pairs of adjacent electrodes. A time-frequency analysis based on Morlet wavelet transformation was performed in a [-1 s : 1 s] time interval around the stimulus and a frequency range of 10-520 Hz. Significant (P = 0.05) changes in power spectra averaged for 10 epochs were computed, resulting in event-related spectral perturbation images. In these images, time-frequency analysis of single pulse-evoked responses, in the range of 10-80 Hz for spikes, 80-250 Hz for ripples and 250-520 Hz for fast ripples, were scored by two observers independently. Sensitivity, specificity and predictive value of time-frequency single pulse-evoked responses in the three frequency ranges were compared with seizure onset zone and post-surgical outcome. In all patients, evoked responses included spikes, ripples and fast ripples. For the seizure onset zone, the median sensitivity of time-frequency single pulse-evoked responses decreased from 100% for spikes to 67% for fast ripples and the median specificity increased from 17% for spikes to 79% for fast ripples. A median positive predictive value for the evoked responses in the seizure onset zone of 17% was found for spikes, 26% for ripples and 37% for fast ripples. Five out of seven patients with <50% of fast ripples removed by resection had a poor outcome. A wavelet transform-based time-frequency analysis of single pulse electrical stimulation reveals evoked responses in the frequency range of spikes, ripples and fast ripples. We demonstrate that time-frequency analysis of single pulse electrical stimulation can assist in delineation of the epileptogenic cortex using time-frequency single pulse-evoked fast ripples as a potential new marker.

High-resolution source imaging in mesiotemporal lobe epilepsy: a comparison between MEG and simultaneous EEG.

Summary Magnetic source imaging is claimed to have a high accuracy in epileptic focus localization and may be a guide for epilepsy surgery. Non-lesional mesiotemporal lobe epilepsy (MTLE), the most common form of epilepsy operated on, has different etiologies, which may affect the choice of surgical approach. The authors compared whole-head magnetoencephalography (MEG) with high-resolution EEG for source identification in MTLE. Nineteen patients with unilateral, nonlesional MTLE underwent a simultaneous 151-channel CTF MEG (CTF Systems, Inc., Port Coquitlam, British Columbia, Canada) and 64-channel EEG recordings with sleep induction. Three independent observers selected spikes from the EEG and MEG recordings separately. Only when there was interobserver agreement (kappa>0.4) on the presence of spikes in recordings were consensus spikes averaged. EEG and MEG equivalent current dipoles (ECD) were then integrated in the head model of the patient reconstructed from MRI. The results were compared with intraoperative electrocorticography findings. Spikes were detected in 32% of MEGs and 42% of EEGs. No patient showed MEG spikes only. Equivalent current dipole modeling correctly localized the source to the temporal lobe in four out of five MEG and three out of eight EEG recordings. MEG localized sources were more superficial and EEG localized sources were deeper. Unfortunately, basal temporal lobe areas were only partially covered by the sensor helmet of the MEG setup. Best correlation between EEG or MEG findings and electrocorticography findings was between horizontal EEG dipole orientation and prominent neocortical spiking; these patients also had a less favorable prognosis. Magnetic source imaging is currently unlikely to alter the surgical management of MTLE. The yield of spikes is too low, and ECD modeling shows only partial correlation with electrocorticography findings. Moreover, the whole-head MEG helmet provides insufficient coverage of the temporal lobe.