Eva K. Ritzl

Effect of an External Responsive Neurostimulator on Seizures and Electrographic Discharges during Subdural Electrode Monitoring

Summary:  Purpose: Approved neural‐stimulation therapies for epilepsy use prolonged intermittent stimulation paradigms with no ability to respond automatically to seizures.

Atypical language in lesional and nonlesional complex partial epilepsy

Objective: We investigated the relationship between partial epilepsy, MRI findings, and atypical language representation. Methods: A total of 102 patients (4 to 55 years) with left hemisphere epileptogenic zones were evaluated using three fMRI language tasks obtained at 1.5 or 3T with EPI BOLD techniques: verbal fluency, reading comprehension, and auditory comprehension. fMRI maps were visually interpreted at a standard threshold and rated as left or atypical language. Results: Atypical language dominance occurred in 30 patients (29%) and varied with MRI type (p < 0.01). Atypical language representation occurred in 36% (13/36) with normal MRI, 21% (6/29) with mesial temporal sclerosis, 14% (4/28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and all (6/6) with a history of stroke. Multivariate logistic regression analysis found handedness, seizure onset, and MRI type accounted for much of the variance in language activation patterns (χ2 = 24.09, p < 0.01). Atypical language was more prevalent in patients with early seizure onset (43.2%, p < 0.05) and atypical handedness (60%, p < 0.01). None of the three clinical factors were correlated with each other (p > 0.40). Patients with atypical language had lower verbal abilities (F = 6.96, p = 0.01) and a trend toward lower nonverbal abilities (F = 3.58, p = 0.06). There were no differences in rates of atypical language across time, age groups, or MRI scanner. Conclusion: Early seizure onset and atypical handedness, as well as the location and nature of pathologic substrate, are important factors in language reorganization. GLOSSARY: FOV = field of view; MTS = mesial temporal sclerosis; RRN = read response naming; TE = echo time; TR = repetition time; WAIS = Wechsler Adult Intelligence Scale; WISC = Wechsler Intelligence Scale for Children.

The fMRI Success Rate of Children and Adolescents: Typical Development, Epilepsy, Attention Deficit/Hyperactivity Disorder, and Autism Spectrum Disorders

Functional magnetic resonance imaging (fMRI) in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with epilepsy, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%; ASD, 70%; TYP, 87%). Ten to 18‐year‐old had a significantly greater scan success rate than 4‐ to 6‐year‐old; adolescents (13‐ to 18‐year‐old) demonstrated greater scan success rates than 7‐ to 9‐year‐old. Success rate for completing an entire battery of experimental runs (n = 2–6), varied between 50–59% for patient populations and 69% for TYP (79% when excluding 4‐ to 6‐year‐old). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20–30% more children should be recruited in these patient groups, but only 10–20% for TYP for research studies. Studies with 4‐ to 6‐year‐olds may require 20–40% additional participants; studies with 10‐ to 18‐year‐olds may require 10–15% additional participants. Hum Brain Mapp, 2009.

Usefulness of pulsed arterial spin labeling MR imaging in mesial temporal lobe epilepsy

PURPOSE Arterial spin labeling (ASL) is a developing magnetic resonance imaging (MRI) method for noninvasive measurement of cerebral blood flow (CBF). The purpose of this study was to evaluate the usefulness of ASL for detecting interictal temporal hypoperfusion in temporal lobe epilepsy (TLE). ASL-derived CBF measurements were compared with those derived from H(2)(15)O positron emission tomography (PET). METHODS 11 normal controls and 10 patients with medically intractable TLE were studied. Pulsed ASL (PASL) with quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) was performed in all subjects and H(2)(15)O PET was performed in patients. Regional CBF values in the mesial and lateral temporal lobes were measured utilizing quantitative analysis of perfusion images. A perfusion asymmetry index (AI) was calculated for each region. RESULTS In patients, mean CBF in the mesial temporal lobe was not significantly different between PASL and H(2)(15)O PET, and ipsilateral mesial temporal CBF was lower than contralateral CBF with both techniques. PASL detected significant mesial temporal perfusion asymmetry agreeing with EEG laterality in four patients. H(2)(15)O PET found ipsilateral interictal hypoperfusion in three. Both scans found unilateral hypoperfusion in one patient with bilateral EEG discharges. CONCLUSIONS Pulsed ASL may be a promising approach to detecting interictal hypoperfusion in TLE. This method has potential as a clinical alternative to H(2)(15)O PET due to noninvasiveness and easy accessibility.

Interhemispheric and intrahemispheric language reorganization in complex partial epilepsy

Objective: To investigate interhemispheric and intrahemispheric reorganization in patients with localization-related epilepsy. Method: We studied 50 patients with a left hemispheric focus and 20 normal right-handed controls with a 3T echoplanar imaging blood oxygen level dependent functional MRI auditory-based word definition decision task. Data were analyzed using SPM 2. Using region of interest for Broca and Wernicke areas and an asymmetry index (AI), patients were categorized as left language (LL; AI ≥0.20) or atypical language (AL; AI <0.20) for region. The point maxima activation for normal controls (p <0.05 corrected FDR) was identified in Broca and midtemporal regions and then used as a point of reference for individual point maxima identified at p < 0.001, uncorrected. Results: Patient groups showed increased frequency of having activation in right homologues. Activation in AL groups occurred in homologous right regions; distances for point maxima activation in homologous regions were the same as point maxima distances in normal control activation in left regions. Distances for LL patient in left regions showed a trend for differences for midtemporal gyrus (6 mm posterior, 3 mm superior) but variability around mean difference distance was significant. There was no effect of age at epilepsy onset, duration, or pathology on activation maxima. Conclusions: Right hemisphere language regions in patients with left hemispheric focus are homologues of left hemisphere Broca and broadly defined Wernicke areas. We found little evidence for intrahemispheric reorganization in patients with left hemisphere epilepsy who remain left language dominant by these methods.

Characterization of atypical language activation patterns in focal epilepsy

Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority.

Quantifying Auditory Event-Related Responses in Multichannel Human Intracranial Recordings

Multichannel intracranial recordings are used increasingly to study the functional organization of human cortex. Intracranial recordings of event-related activity, or electrocorticography (ECoG), are based on high density electrode arrays implanted directly over cortex, combining good temporal and spatial resolution. Developing appropriate statistical methods for analyzing event-related responses in these high dimensional ECoG datasets remains a major challenge for clinical and systems neuroscience. We present a novel methodological framework that combines complementary, existing methods adapted for statistical analysis of auditory event-related responses in multichannel ECoG recordings. This analytic framework integrates single-channel (time-domain, time–frequency) and multichannel analyses of event-related ECoG activity to determine statistically significant evoked responses, induced spectral responses, and effective (causal) connectivity. Implementation of this quantitative approach is illustrated using multichannel ECoG data from recent studies of auditory processing in patients with epilepsy. Methods described include a time–frequency matching pursuit algorithm adapted for modeling brief, transient cortical spectral responses to sound, and a recently developed method for estimating effective connectivity using multivariate autoregressive modeling to measure brief event-related changes in multichannel functional interactions. A semi-automated spatial normalization method for comparing intracranial electrode locations across patients is also described. The individual methods presented are published and readily accessible. We discuss the benefits of integrating multiple complementary methods in a unified and comprehensive quantitative approach. Methodological considerations in the analysis of multichannel ECoG data, including corrections for multiple comparisons are discussed, as well as remaining challenges in the development of new statistical approaches.

Sensitivity of quantitative EEG for seizure identification in the intensive care unit

Objective: To evaluate the sensitivity of quantitative EEG (QEEG) for electrographic seizure identification in the intensive care unit (ICU). Methods: Six-hour EEG epochs chosen from 15 patients underwent transformation into QEEG displays. Each epoch was reviewed in 3 formats: raw EEG, QEEG + raw, and QEEG-only. Epochs were also analyzed by a proprietary seizure detection algorithm. Nine neurophysiologists reviewed raw EEGs to identify seizures to serve as the gold standard. Nine other neurophysiologists with experience in QEEG evaluated the epochs in QEEG formats, with and without concomitant raw EEG. Sensitivity and false-positive rates (FPRs) for seizure identification were calculated and median review time assessed. Results: Mean sensitivity for seizure identification ranged from 51% to 67% for QEEG-only and 63%–68% for QEEG + raw. FPRs averaged 1/h for QEEG-only and 0.5/h for QEEG + raw. Mean sensitivity of seizure probability software was 26.2%–26.7%, with FPR of 0.07/h. Epochs with the highest sensitivities contained frequent, intermittent seizures. Lower sensitivities were seen with slow-frequency, low-amplitude seizures and epochs with rhythmic or periodic patterns. Median review times were shorter for QEEG (6 minutes) and QEEG + raw analysis (14.5 minutes) vs raw EEG (19 minutes; p = 0.00003). Conclusions: A panel of QEEG trends can be used by experts to shorten EEG review time for seizure identification with reasonable sensitivity and low FPRs. The prevalence of false detections confirms that raw EEG review must be used in conjunction with QEEG. Studies are needed to identify optimal QEEG trend configurations and the utility of QEEG as a screening tool for non-EEG personnel. Classification of evidence review: This study provides Class II evidence that QEEG + raw interpreted by experts identifies seizures in patients in the ICU with a sensitivity of 63%–68% and FPR of 0.5 seizures per hour.

fMRI language dominance and FDG-PET hypometabolism

Background: Atypical language dominance is common in patients with temporal lobe epilepsy. We examined the association of left temporal hypometabolism with laterality of fMRI activation in a language task in a cross-sectional study. Methods: Thirty patients with temporal lobe epilepsy (mean age 32.4 ± 11.0 years [range 18–55]; epilepsy onset 15.3 ± 11.3 years [range 0.8–40]; 22 left focus, 8 right focus) had 18fluoro-deoxyglucose (FDG)-PET using noninvasive cardiac input function. After MRI-based partial volume correction, regional glucose metabolism (CMRglc) was measured and asymmetry index, AI = 2(l − R)/(L + R), calculated. fMRI language dominance was assessed with an auditory definition decision paradigm at 3 T. fMRI data were analyzed in SPM2 using regions of interest from Wake Forest PickAtlas (Wernicke area [WA], inferior frontal gyrus [IFG], middle frontal gyrus [MFG]) and bootstrap laterality index, LI = (l − R/L + R). Results: Nineteen patients had ipsilateral temporal hypometabolism; 3 of 4 patients with atypical language had abnormal FDG-PET. Increasing left midtemporal hypometabolism correlated with decreased MFG LI (r = −0.41, p < 0.05) and showed trends with WA LI (r = −0.37, p = 0.055) and IFG LI (r = −0.31, p = 0.099); these relationships became more significant after controlling for age at onset. Increasing hypometabolism was associated with fewer activated voxels in WA ipsilateral to the focus and more activated voxels contralaterally, but overall, activation amount in left WA was similar to subjects without left temporal hypometabolism (t = −1.39, p > 0.10). Conclusions: We did not find evidence of impaired blood oxygenation level–dependent response in hypometabolic cortex. Regional hypometabolism appears to be a marker for the temporal lobe dysfunction that leads to displacement of language function.

The effect of seizure focus on regional language processing areas

Purpose:  To determine the effect of seizure focus location within the left hemisphere on the expression of regional language dominance.