Learn how to interpret and use intracranial EEG findings.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.

Examining potential confounding factors in gene expression analysis of human saliva and identifying potential housekeeping genes.

Isolation of RNA from whole saliva, a non-invasive and easily accessible biofluid that is an attractive alternative to blood for high-throughput biodosimetry of radiological/nuclear victims might be of clinical significance for prediction and diagnosis of disease. In a previous analysis of 12 human samples we identified two challenges to measuring gene expression from total RNA: (1) the fraction of human RNA in whole saliva was low and (2) the bacterial contamination was overwhelming. To overcome these challenges, we performed selective cDNA synthesis for human RNA species only by employing poly(A)+-tail primers followed by qRT-PCR. In the current study, this approach was independently validated on 91 samples from 61 healthy donors. Additionally, we used the ratio of human to bacterial RNA to adjust the input RNA to include equal amounts of human RNA across all samples before cDNA synthesis, which then ensured comparable analysis using the same base human input material. Furthermore, we examined relative levels of ten known housekeeping genes, and assessed inter- and intra-individual differences in 61 salivary RNA isolates, while considering effects of demographical factors (e.g. sex, age), epidemiological factors comprising social habits (e.g. alcohol, cigarette consumption), oral hygiene (e.g. flossing, mouthwash), previous radiological diagnostic procedures (e.g. number of CT-scans) and saliva collection time (circadian periodic). Total human RNA amounts appeared significantly associated with age only (P ≤ 0.02). None of the chosen housekeeping genes showed significant circadian periodicity and either did not associate or were weakly associated with the 24 confounders examined, with one exception, 60% of genes were altered by mouthwash. ATP6, ACTB and B2M represented genes with the highest mean baseline expression (Ct-values ≤ 30) and were detected in all samples. Combining these housekeeping genes for normalization purposes did not decrease inter-individual variance, but increased the robustness. In summary, our work addresses critical confounders and provides important information for the successful examination of gene expression in human whole saliva.

Early molecular markers for retrospective biodosimetry and prediction of acute health effects.

Radiation-induced biological changes occurring within hours and days after irradiation can be potentially used for either exposure reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of molecular protein or gene expression (GE) (mRNA) marker lies in their capability for early (1-3 days after irradiation), high-throughput and point-of-care diagnosis, required for the prediction of the acute radiation syndrome (ARS) in radiological or nuclear scenarios. These molecular marker in most cases respond differently regarding exposure characteristics such as e.g. radiation quality, dose, dose rate and most importantly over time. Changes over time are in particular challenging and demand certain strategies to deal with. With this review, we provide an overview and will focus on already identified and used mRNA GE and protein markers of the peripheral blood related to the ARS. These molecules are examined in light of 'ideal' characteristics of a biomarkers (e.g. easy accessible, early response, signal persistency) and the validation degree. Finally, we present strategies on the use of these markers considering challenges as their variation over time and future developments regarding e.g. origin of samples, point of care and high-throughput diagnosis.

Hippocampal size anomalies in a community-based cohort with childhood-onset epilepsy.

OBJECTIVES: Epidemiologic evidence suggests the natural history of refractory mesial temporal lobe epilepsy is complicated, yet little is known about the hippocampus from the nontertiary center perspective. METHODS: In a community-based cohort, individuals with nonsyndromic focal epilepsy with onset <16 years and controls had research MRI scans. Hippocampal (HC) volumes were manually measured, corrected for total brain volume, and converted to Z scores (Z(HC)) based on the controls' values. Volumes in cases and controls were compared. RESULTS: Average volumes were not significantly different in cases with unknown cause (n = 117) relative to controls (n = 63). The group with structural and other conditions (n = 23) had significantly smaller volumes. Asymmetry (larger/smaller HC) did not vary among the 3 groups. Hippocampal variances were significantly larger in each epilepsy group relative to controls. In the unknown cause group, 25 (21%) had extreme() values: 15 (13%) with Z(HC) >1.96; 10 (9%) with Z(HC) <-1.96. By contrast, 2/63 (3%) controls had extreme values (p = 0.001). Within the unknown cause group, temporal lobe epilepsy (TLE) cases were more likely to have extreme hippocampal volumes than non-TLE (31% vs 15%, p = 0.03). Extreme volumes were generally interpreted as normal visually. These anomalies were not associated with seizure remission or pharmacoresistance. CONCLUSIONS: Classic mesial TLE with hippocampal sclerosis is an uncommon finding in the general population. Volume anomalies, both large and small, are often bilateral. The significance of these findings is unclear; however, speculations regarding preexisting hippocampal pathology (e.g., dysplasia) as a factor in TLE and other neocortical epilepsies have been made by others.

Visual naming performance after ATL resection: impact of atypical language dominance.

PURPOSE: To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL). METHODS: Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus. RESULTS: Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size=0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n=14; p<0.05), but did not reach statistical significance in patients with left language dominance (n=36; p=0.09). Chi-square test revealed a trend of higher proportions of patients experiencing significant postsurgical deterioration in naming performance in atypical (57.1%) as compared to left language dominance (30.6%; p=0.082). Surgical failure was also associated with greater decline of BNT scores and was more common in atypical than in left language dominant patients (chi(2) (1, n=98)=4.62, p=0.032). Age of onset, duration of epilepsy, and seizure frequency had no impact on changes in BNT performance. CONCLUSION: Atypical language dominance is a predictor of change in visual naming performance after left ATL and may also impact postsurgical seizure control. This should be considered when counseling surgical candidates.

Memory performance is related to language dominance as determined by the intracarotid amobarbital procedure.

OBJECTIVE: The goal of this study was to explore the relationship between language and memory lateralization in patients with epilepsy undergoing the intracarotid amobarbital procedure. METHODS: In 386 patients, language lateralization and memory lateralization as determined by laterality index (LI) were correlated with each other. RESULTS: Language lateralization and memory lateralization were positively correlated (r=0.34, P<0.01). Correlations differed depending on the presence and type of lesion (chi(2)=7.98, P<0.05). LIs correlated significantly higher (z=2.82, P<0.05) in patients with cortical dysplasia (n=41, r=0.61, P<0.01) compared with the group without lesions (n=90, r=0.16, P>0.05), with patients with hippocampal sclerosis falling between these two groups. Both memory (P<0.01) and language (P<0.01) LIs were higher in right- compared with left-sided lesions. CONCLUSION: Correlation of language and memory is more pronounced in patients with structural lesions as compared with patients without lesions on MRI.

Evidence for a basal temporal visual language center: cortical stimulation producing pure alexia.

BACKGROUND: Dejerine and Benson and Geschwind postulated disconnection of the dominant angular gyrus from both visual association cortices as the basis for pure alexia, emphasizing disruption of white matter tracts in the dominant temporooccipital region. Recently functional imaging studies provide evidence for direct participation of basal temporal and occipital cortices in the cognitive process of reading. The exact location and function of these areas remain a matter of debate. OBJECTIVE: To confirm the participation of the basal temporal region in reading. METHOD: Extraoperative electrical stimulation of the dominant hemisphere was performed in three subjects using subdural electrodes, as part of presurgical evaluation for refractory epilepsy. RESULTS: Pure alexia was reproduced during cortical stimulation of the dominant posterior fusiform and inferior temporal gyri in all three patients. Stimulation resulted in selective reading difficulty with intact auditory comprehension and writing. Reading difficulty involved sentences and words with intact letter by letter reading. Picture naming difficulties were also noted at some electrodes. This region is located posterior to and contiguous with the basal temporal language area (BTLA) where stimulation resulted in global language dysfunction in visual and auditory realms. The location corresponded with the visual word form area described on functional MRI. CONCLUSION: These observations support the existence of a visual language area in the dominant fusiform and occipitotemporal gyri, contiguous with basal temporal language area. A portion of visual language area was exclusively involved in lexical processing while the other part of this region processed both lexical and nonlexical symbols.

Video-electrographic and clinical features in patients with ictal asystole.

OBJECTIVE: Ictal asystole (IA) is a rare event mostly seen in patients with temporal lobe epilepsy (TLE) and a potential contributor to sudden unexplained death in epilepsy (SUDEP). Clinical and video-electroencephalographic findings associated with IA have not been described, and may be helpful in screening for high risk patients. METHODS: A database search was performed of 6,825 patients undergoing long-term video-EEG monitoring for episodes of IA. RESULTS: IA was recorded in 0.27% of all patients with epilepsy, eight with temporal (TLE), two with extratemporal (XTLE), and none with generalized epilepsy. In 8 out of 16 recorded events, all occurring in patients with TLE, seizures were associated with a sudden atonia on average 42 seconds into the typical semiology of a complex partial seizure. The loss of tone followed after a period of asystole usually lasting longer than 8 seconds and was associated with typical EEG changes seen otherwise with cerebral hypoperfusion. Clinical predisposing factors for IA including cardiovascular risk factors or baseline ECG abnormalities were not identified. CONCLUSION: Ictal asystole is a rare feature of patients with focal epilepsy. Delayed loss of tone is distinctly uncommon in patients with temporal lobe seizures, but may inevitably occur in patients with ictal asystole after a critical duration of cardiac arrest and cerebral hypoperfusion. Further cardiac monitoring in patients with temporal lobe epilepsy and a history of unexpected collapse and falls late in the course of a typical seizure may be warranted and can potentially help to prevent sudden unexplained death in epilepsy.

[Suggestion for a new, patient-oriented epilepsy classification]. / Vorschlag für eine neue patientenorientierte Epilepsieklassifikation.

The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

Incidence of seizures in patients with multiple sclerosis treated with intrathecal baclofen.

Oral and intrathecal baclofen (ITB) have been associated with epileptic seizures. The authors observed a higher incidence of epileptic seizures in 99 patients with multiple sclerosis (MS) treated with ITB vs a matched control group (7% vs 1%, p < 0.05). Three patients with MS on ITB developed status epilepticus. Seizures were often associated with additional triggering factors.

A rapid method to quantify left atrial contractile function: Doppler tissue imaging of the mitral annulus during atrial systole.

AIMS: Assess the value of peak atrial systolic mitral annular velocity (Aann) measured by Doppler tissue echocardiography to quantify left atrial systolic function. METHODS: We studied a total of 61 adults; 10 subjects without history of heart disease and 51 patients with a history of atrial fibrillation or undergoing evaluation for left ventricular systolic or diastolic dysfunction. Aann was obtained by averaging peak atrial systolic mitral annular velocities from the septal, lateral, anterior, and inferior annulus. Left atrial fractional area change (FAC) and fractional volume change (FVC) during atrial systole were calculated. The correlation between peak atrial systolic mitral annular velocity (Aann) and left atrial systolic FAC and FVC was determined. RESULTS: Mean FAC and FVC were 27 +/- 12 and 40 +/- 14%, respectively; mean Aann was 11.2 +/- 3.2 cm/s. Linear regression analysis showed correlation between Aann and FAC (r = 0.71; p<0.001) and between Aann and FVC (r = 0.74; p<0.001). CONCLUSIONS: Peak systolic mitral annular velocity correlates well with left atrial systolic FAC and FVC, thus providing an easy means to assess left atrial systolic function.

Complications of gamma knife surgery for Parkinson disease.

BACKGROUND: Many medical centers throughout the world offer radiosurgery with the gamma knife (GK) for pallidotomy and thalamotomy as a safe and effective alternative to radiofrequency ablative surgery and deep brain stimulation for Parkinson disease (PD). The reported incidence of significant complications varies considerably, and the long-term complication rate remains unknown. DESIGN: We describe 8 patients seen during an 8-month period referred for complications of GK surgery for PD. RESULTS: Of the 8 patients, 1 died as a result of complications, including dysphagia and aspiration pneumonia. Other complications included hemiplegia, homonymous visual field deficit, hand weakness, dysarthria, hypophonia, aphasia, arm and face numbness, and pseudobulbar laughter. In all patients, lesions were significantly off target. CONCLUSIONS: The 8 patients with PD seen in referral at our center for complications of GK surgery highlight a spectrum of potential problems associated with this procedure. These include lesion accuracy and size and the delayed development of neurological complications secondary to radiation necrosis. Gamma knife surgery may have a higher complication rate than has been previously appreciated due to delayed onset and underreporting. We believe that the risk-benefit ratio of the GK will require further scrutiny when considering pallidotomy or thalamotomy in patients with PD. Physicians using this technique should carefully follow up patients postoperatively for delayed complications, and fully inform patients of these potential risks.

Expression of the rat liver Na+/taurocholate cotransporter is regulated in vivo by retention of biliary constituents but not their depletion.

Expression and function of the hepatic Na+/taurocholate cotransporter (ntcp) are down-regulated in several models of experimental cholestasis. To test whether retention and/or depletion of biliary constituents are involved in ntcp regulation, ntcp expression was quantified in several animal models with altered levels of these constituents. In choledochocaval fistula rats (CCF) (retention model), ntcp mRNA expression specifically declined after 1 and 3 days by 76 +/- 4% (P < .005) and 31 +/- 9% (P < .05), respectively, returning to control levels by 7 days. However, protein expression as assessed by Western blotting remained unchanged for up to 7 days of CCF. In rats with bile fistulas (depletion model) for 0.5, 1, 2, 4, and 7 days, both ntcp protein and mRNA expression remained unaltered. Infusion of either taurocholate or taurochenodeoxycholate for 12 hours also did not effect ntcp mRNA expression in intact animals, probably because of its inability to increase serum and intrahepatic bile acid levels. In rats with selective bile duct ligation (SBDL), ntcp mRNA levels were down-regulated by 40 +/- 10% (P < .05) only after 12 and 24 hours in ligated lobes, and mRNA levels returned to control values in these lobes after 2 and 4 days. ntcp mRNA expression remained unchanged in the nonobstructed lobes at any time. When data from CCF and SBDL rats were combined, serum bile acids correlated linearly with ntcp mRNA (r = .62, P < .0005) over a 0 to 110-micromol/L range. Our results indicate that ntcp is constitutively expressed and remains uneffected by either depletion or increased flux of biliary constituents. However, retention of biliary constituents results in rapid down-regulation of ntcp mRNA, consistent with the concept that hepatocytes may be protected from bile acid toxicity during cholestasis by this mechanism.

Down-regulation of expression and function of the rat liver Na+/bile acid cotransporter in extrahepatic cholestasis.

BACKGROUND & AIMS: The molecular regulation of hepatic bile acid transporters during cholestasis is largely unknown. Cloning of complementary DNAs for the sinusoidal sodium-dependent taurocholate cotransporting polypeptide (ntcp), the cytosolic bile acid-binding protein 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), and a putative canalicular bile acid transporter Ca2+, Mg(2+)-ecto-adenosine triphosphatase, now facilitates such studies. METHODS: Protein mass, steady-state messenger RNA (mRNA) levels, and gene transcription were assessed in rat livers after common bile duct ligation (CBDL) from 1-7 days, and taurocholate uptake was determined in isolated hepatocytes. RESULTS: After CBDL, Na(+)-dependent taurocholate uptake (Vmax) declined by 70%. The levels of ntcp protein were reduced by more than 90%, and 3 alpha-HSD levels decreased by 66% by 7 days. Expression and canalicular localization of the ecto-adenosine triphosphatase remained unchanged. mRNA levels for both ntcp and 3 alpha-HSD diminished by about 60% 1 day after CBDL and remained unchanged up to 7 days. Transcriptional activity was decreased 1 day after CBDL only for ntcp. CONCLUSIONS: Extrahepatic cholestasis results in rapid down-regulation of Na(+)-dependent taurocholate uptake, ntcp transcription, and posttranscriptional regulation of both ntcp and 3 alpha-HSD mRNA. This selective decline of ntcp may represent a protective feedback mechanism in cholestasis to diminish uptake of potentially hepatotoxic bile acids.