A systems-level approach to human epileptic seizures.

Epileptic seizures are due to the pathological collective activity of large cellular assemblies. A better understanding of this collective activity is integral to the development of novel diagnostic and therapeutic procedures. In contrast to reductionist analyses, which focus solely on small-scale characteristics of ictogenesis, here we follow a systems-level approach, which combines both small-scale and larger-scale analyses. Peri-ictal dynamics of epileptic networks are assessed by studying correlation within and between different spatial scales of intracranial electroencephalographic recordings (iEEG) of a heterogeneous group of patients suffering from pharmaco-resistant epilepsy. Epileptiform activity as recorded by a single iEEG electrode is determined objectively by the signal derivative and then subjected to a multivariate analysis of correlation between all iEEG channels. We find that during seizure, synchrony increases on the smallest and largest spatial scales probed by iEEG. In addition, a dynamic reorganization of spatial correlation is observed on intermediate scales, which persists after seizure termination. It is proposed that this reorganization may indicate a balancing mechanism that decreases high local correlation. Our findings are consistent with the hypothesis that during epileptic seizures hypercorrelated and therefore functionally segregated brain areas are re-integrated into more collective brain dynamics. In addition, except for a special sub-group, a highly significant association is found between the location of ictal iEEG activity and the location of areas of relative decrease of localised EEG correlation. The latter could serve as a clinically important quantitative marker of the seizure onset zone (SOZ).

Forbidden ordinal patterns of periictal intracranial EEG indicate deterministic dynamics in human epileptic seizures.

PURPOSE: Epileptic seizures typically reveal a high degree of stereotypy, that is, for an individual patient they are characterized by an ordered and predictable sequence of symptoms and signs with typically little variability. Stereotypy implies that ictal neuronal dynamics might have deterministic characteristics, presumably most pronounced in the ictogenic parts of the brain, which may provide diagnostically and therapeutically important information. Therefore the goal of our study was to search for indications of determinism in periictal intracranial electroencephalography (EEG) studies recorded from patients with pharmacoresistent epilepsy. METHODS: We assessed the number of forbidden ordinal patterns of 110 periictal multichannel intracranial EEG studies of 16 patients. Ordinal patterns are derived from the rank order of short sequences of consecutive EEG values. Ordinal patterns are well suited for analyzing real-world time series, for they have low sensitivity for many forms of noise and are applicable to nonstationary data. Although Gaussian random dynamics generate all possible ordinal patterns for a given sequence length, deterministic dynamics typically manifest with less random and more regular signals that miss a certain number of all the possible ordinal patterns. These missing ordinal patterns are referred to as "forbidden ordinal patterns." In this study, the number of forbidden ordinal patterns n(fp) of an EEG signal was interpreted as an indication of determinism, when it was larger than the number of forbidden patterns occurring in amplitude adjusted Fourier transform surrogates. We computed n(fp) for each EEG signal in a time-resolved way by using a moving-window approach. Then we specifically investigated n(mean)(fp) denoting the average number of forbidden patterns across all EEG signals, and n(max)(fp), which represents the number of forbidden patterns occurring in the EEG signal with the largest n(fp) during the seizure-onset period. KEY FINDINGS: The average number of forbidden patterns of all EEG signals, n(mean)(fp), typically first increased and then decreased during the seizures. However, these changes were not statistically significant relative to the preseizure time period. In contrast, n(max)(fp)typically increased significantly during the first third of the seizure period and then gradually decreased toward and beyond seizure termination. In those patients who became seizure free following surgery, a larger percentage of the EEG signals containing the maximal number of forbidden patterns during the seizure-onset period tended to be recorded from within the visually identified seizure-onset zones. SIGNIFICANCE: Our findings demonstrate a spatiotemporally limited shift of neuronal dynamics toward a more deterministic dynamic regimen, specifically pronounced during the seizure-onset period. Assessing the number of forbidden ordinal patterns of intracranial EEG provides quantitative and observer-independent information. We propose that it is at least partially complementary to classical visual EEG reading and may be diagnostically helpful to better delineate ictogenic parts of the brain.

Glycogen-rich pleomorphic xanthoastrocytoma with clear-cell features: confirmatory report of a rare variant with implications for differential diagnosis.

Central nervous system space-occupying lesions with clear-cell features encompass a nosologically heterogeneous array, ranging from reactive histiocytic proliferations to neuroepithelial or meningothelial neoplasms of various grades and to metastases. In the face of such differential diagnostic breadth, recognizing cytoplasmic lucency as part of the morphological spectrum of some low grade gliomas will directly have an impact on patient care. We describe a prevailing clear-cell change in an epileptogenic left temporal pleomorphic xanthoastrocytoma surgically resected from a 36-year-old man. Mostly subarachnoid and focally calcified, the tumor was composed of fascicles of moderately atypical spindle cells with optically lucent cytoplasm that tended to intermingle with a desmoplastic mesh of reticulin fibers. Immunohistochemically, coexpression of S100 protein, vimentin, GFAP, and CD34 was noted. Conversely, neither punctate staining for EMA nor positivity for CD68 was seen. Mitotic activity was absent, and the MIB1 labeling index was 2-3% on average. Diastase-sensitive PAS-positive granula indicated clear-cell change to proceed from glycogen storage. Electron microscopy showed tumor cell cytoplasm to be largely obliterated by non-lysosomal-bound pools of glycogen, while hardly any fat vacuole was encountered. Neither ependymal-derived organelles nor annular lamellae suggesting oligodendroglial differentiation were detected. The latter differential diagnosis was further invalidated by lack of codeletion of chromosomal regions 1p36 and 19q13 on molecular genetic testing. By significantly interfering with pattern recognition as an implicit approach in histopathology, clear-cell change in pleomorphic xanthoastrocytoma is likely to suspend its status as a "classic", and to prompt more deductive differential diagnostic strategies to exclude look-alikes, especially clear-cell ependymoma and oligodendroglioma.

Peri-ictal correlation dynamics of high-frequency (80-200 Hz) intracranial EEG.

PURPOSE: To assess (1) how large-scale correlation of intracranial EEG signals in the high-frequency range (80-200Hz) evolves from the pre-ictal, through the ictal into the postictal state and (2) whether the contribution of local neuronal activity to large-scale EEG correlation differentiates epileptogenic from non-epileptogenic brain tissue. METHODS: Large-scale correlation of intracranial EEG was assessed by the total correlation strength (TCS), a measure derived from the eigenvalue spectra of zero-lag correlation matrices computed in a time-resolved manner by using a moving window approach. The relative change of total correlation strength (Delta(j)) resulting from leaving out EEG channel j ("leave-one-out approach") was used to quantify the contribution of local neuronal activity to large-scale EEG correlation. RESULTS: 19 seizures of 3 patients were analyzed. On average, TCS increased significantly from the pre-ictal to the ictal, and from the ictal to the postictal state. In the pre-ictal state, Delta(j) was significantly more negative when EEG channels that recorded the electrical activity of brain tissue considered to be epileptogenic were left out; the identification of the epileptogenic area, that was subsequently surgically removed in two patients, was based on visual analysis. The spatio-temporal pattern of Delta(j) dramatically changed at seizure onsets and endings, revealing qualitative similarities between the seizures of different patients. DISCUSSION: The evolution of large-scale EEG correlation in the high-frequency range is qualitatively similar to the one previously described for the low-frequency range. Because the two patients who underwent surgery became seizure free, our findings are consistent with the hypothesis that epileptogenic brain tissue may be characterized by its relatively increased contribution to pre-ictal large-scale correlation.

Effect of thalamic deep brain stimulation on lower urinary tract function.

OBJECTIVE: The precise mechanisms underlying cerebral regulation of lower urinary tract function are still poorly understood. In patients with disabling essential tremor (ET) refractory to pharmacotherapy, thalamic deep brain stimulation (DBS) is an effective treatment for tremor control. Here, we evaluated the effect of thalamic DBS on urodynamic parameters in patients with ET. PATIENTS AND METHODS: We investigated seven patients (two females, five males) with ET 15-85 mo after implantation of DBS leads into the ventral intermediate nucleus of the thalamus. We compared urodynamic parameters during thalamic DBS (ON state) and 30 min after turning the stimulator off (OFF state). RESULTS: In the ON compared with the OFF state, there was a significant decrease in bladder volume at first desire to void (median, 218 ml vs. 365 ml, p=0.031), at strong desire to void (median, 305 ml vs. 435 ml, p=0.031), and at maximum cystometric capacity (median, 345 ml vs. 460 ml, p=0.016). No significant differences between the ON and OFF state were detected for changes in detrusor pressure during filling cystometry, bladder compliance, maximum detrusor pressure, detrusor pressure at maximum flow rate, maximum flow rate, voided volume, and postvoid residual. CONCLUSIONS: Thalamic deep brain stimulation resulted in an earlier desire to void and decreased bladder capacity, suggesting a regulatory role of the thalamus in lower urinary tract function. Therefore, the thalamus may be a promising target for the development of new therapies for lower urinary tract dysfunction.

Echinococcosis presenting as an otogenic brain abscess: an unusual lesion of the middle ear cleft and temporal lobe.

This paper presents a case of a 28-year-old male with a seizure episode and a 4-year history of intermittent tinnitus on the left ear. On computed tomography and magnetic resonance imaging, a density with rim enhancement was found at the temporal lobe, associated with mastoid tegmen destruction and middle ear mass, indicating cholesteatoma with complicating brain abscess. Evacuation of the brain abscess was performed with a combined otolaryngologic and neurosurgical procedures (canal wall-down mastoidectomy and temporal craniotomy). The pathology turned out to be infestation with Echinococcus granulosus.