Rafeed Alkawadri

The spatial and signal characteristics of physiologic high frequency oscillations

To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network.

Cingulate Epilepsy: Report of 3 Electroclinical Subtypes With Surgical Outcomes

IMPORTANCE The literature on cingulate gyrus epilepsy in the magnetic resonance imaging era is limited to case reports and small case series. To our knowledge, this is the largest study of surgically confirmed epilepsy arising from the anterior or posterior cingulate region. OBJECTIVE To characterize the clinical and electrophysiological findings of epilepsies arising from the anterior and posterior cingulate gyrus. DESIGN, SETTING, AND PARTICIPANTS We studied consecutive cingulate gyrus epilepsy cases identified retrospectively from the Cleveland Clinic and University of Texas Southwestern Medical Center epilepsy databases from 1992 to 2009. Participants included 14 consecutive cases of cingulate gyrus epilepsies confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. MAIN OUTCOMES AND MEASURES The main outcome measure was improvement in seizure frequency following surgery. The clinical, video electroencephalography, neuroimaging, pathology, and surgical outcome data were reviewed. RESULTS All 14 patients had cingulate epilepsy confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. They were divided into 3 groups based on anatomical location of the lesion and corresponding seizure semiology. In the posterior cingulate group, all 4 patients had electroclinical findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a typical (Bancaud) group (6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or severe interictal personality changes) and an atypical group (4 cases presenting with simple motor seizures and a tendency for more frequent generalization and less-favorable long-term surgical outcome). All atypical cases were associated with an underlying infiltrative astrocytoma. CONCLUSIONS AND RELEVANCE Posterior cingulate gyrus epilepsy may present with electroclinical findings that are suggestive of temporal lobe epilepsy and can be considered as another example of pseudotemporal epilepsies. The electroclinical presentation and surgical outcome of lesional anterior cingulate epilepsy is possibly influenced by the underlying pathology. This study highlights the difficulty in localizing seizures arising from the cingulate gyrus in the absence of a magnetic resonance image lesion.

Cingulate Gyrus Epilepsy: Clinical and Behavioral Aspects, With Surgical Outcomes

BACKGROUND Cingulate gyrus epilepsy is controversial because it may overlap with other frontal lobe epilepsy syndromes. Reported cases are rare in the pre-magnetic resonance imaging literature but are more common thereafter. Information about peri-ictal and ictal behaviors is scarce. OBJECTIVES To characterize epilepsy originating from the cingulate gyrus and to report surgical outcomes. DESIGN Case studies. SETTING Academic research. PATIENTS We report 3 surgically treated cases of cingulate gyrus epilepsy, with seizure-free or almost seizure-free outcomes. The cases were identified from a database of 4201 consecutive epilepsy monitoring unit admissions since October 1998 through September 2008. All 3 cases involved cingulate lesions. MAIN OUTCOME MEASURES Neuroimaging, video electroencephalographic, pathologic, and surgical outcome data were reviewed. RESULTS All 3 patients had lesional left anterocingulate seizures confirmed by magnetic resonance imaging and experienced cessation of seizures after lesionectomy. Two patients had auras (fear and laughter) previously associated with cingulate gyrus epilepsy. All patients had clinical features consistent with frontal lobe epilepsy, including hyperkinetic behavior and ictal vocalization. Two patients had behavioral changes with aggression, personality disorder, and poor judgment; some behavioral episodes lasted for days and were socially devastating. One patient, a commercial pilot, showed behavior as a passenger that resulted in a diversionary landing. The other patient demonstrated behavior that led to his arrest, and he was almost arrested again in the hospital for threatening security officers. Aberrant behaviors in all 3 patients completely resolved after lesionectomy. CONCLUSIONS Lesional cingulate gyrus epilepsy is uncommon. Our 3 confirmed cases included 2 patients with unique and severe behavioral changes that resolved with lesionectomy.

Automatic detection of prominent interictal spikes in intracranial EEG: validation of an algorithm and relationsip to the seizure onset zone.

OBJECTIVE To develop an algorithm for the automatic quantitative description and detection of spikes in the intracranial EEG and quantify the relationship between prominent spikes and the seizure onset zone. METHODS An algorithm was developed for the quantification of time-frequency properties of spikes (upslope, instantaneous energy, downslope) and their statistical representation in a univariate generalized extreme value distribution. Its performance was evaluated in comparison to expert detection of spikes in intracranial EEG recordings from 10 patients. It was subsequently used in 18 patients to detect prominent spikes and quantify their spatial relationship to the seizure onset area. RESULTS The algorithm displayed an average sensitivity of 63.4% with a false detection rate of 3.2 per minute for the detection of individual spikes and an average sensitivity of 88.6% with a false detection rate of 1.4% for the detection of intracranial EEG contacts containing the most prominent spikes. Prominent spikes occurred closer to the seizure onset area than less prominent spikes but they overlapped with it only in a minority of cases (3/18). CONCLUSIONS Automatic detection and quantification of the morphology of spikes increases their utility to localize the seizure onset area. Prominent spikes tend to originate mostly from contacts located in the close vicinity of the seizure onset area rather than from within it. SIGNIFICANCE Quantitative analysis of time-frequency characteristics and spatial distribution of intracranial spikes provides complementary information that may be useful for the localization of the seizure-onset zone.

Sensitivity of scalp 10-20 EEG and magnetoencephalography

Although previous studies have investigated the sensitivity of electroencephalography (EEG) and magnetoencephalography (MEG) to detect spikes by comparing simultaneous recordings, there are no published reports that focus on the relationship between spike dipole orientation or sensitivity of scalp EEG/MEG and the “gold standard” of intracranial recording (stereotactic EEG). We evaluated two patients with focal epilepsy; one with lateral temporal focus and the other with insular focus. Two MEG recordings were performed for both patients, each recorded simultaneously with initially scalp EEG, based on international 10–20 electrode placement with additional electrodes for anterior temporal regions, and subsequently stereotactic EEG. Localisation of MEG spike dipoles from both studieswas concordant and all MEG spikes were detected by stereotactic EEG. For the patient with lateral temporal epilepsy, spike sensitivity of MEG and scalp EEG (relative to stereotactic EEG) was 55 and 0%, respectively. Of note, in this case, MEG spike dipoles were oriented tangentially to scalp surface in a tight cluster; the angle of the spike dipole to the vertical line was 3.6 degrees. For the patient with insular epilepsy, spike sensitivity of MEG and scalp EEG (relative to stereotactic EEG) was 83 and 44%, respectively; the angle of the spike dipole to the vertical line was 45.3 degrees. For the patient with lateral temporal epilepsy, tangential spikes from the lateral temporal cortex were difficult to detect based on scalp 10–20 EEG and for the patient with insular epilepsy, it was possible to evaluate operculum insular sources using MEG.We believe that these findings may be important for the interpretation of clinical EEG and MEG.

Presurgical language fMRI: Mapping of six critical regions

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Brocas and Wernickes areas, although multiple other language‐critical areas are now well‐known. We evaluated whether clinicians could use a novel approach, including clinician‐driven individualized thresholding, to reliably identify six language regions, including Brocas Area, Wernickes Area (inferior, superior), Exners Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly thresholded and combined these to identify the six regions. The resulting maps were compared to fixed threshold maps. Clinicians generated maps that overlapped significantly, and were highly consistent, when at least one task came from the same set. Cases diverged when clinicians prioritized different language regions or addressed noise differently. Language laterality closely mirrored Wada data (85% accuracy). Activation consistent with all six language regions was consistently identified. In blind review, three external, independent clinicians rated the individualized fMRI language maps as superior to fixed threshold maps; identified the majority of regions significantly more frequently; and judged language laterality to mirror Wada lateralization more often. These data provide initial validation of a novel, clinician‐based approach to localizing language cortex. They also demonstrate clinical fMRI is superior when analyzed by an experienced clinician and that when fMRI data is of low quality judgments of laterality are unreliable and should be withheld. Hum Brain Mapp 38:4239–4255, 2017.

The relationship between seizures, interictal spikes and antiepileptic drugs

OBJECTIVE A considerable decrease in spike rate accompanies antiepileptic drug (AED) taper during intracranial EEG (icEEG) monitoring. Since spike rate during icEEG monitoring can be influenced by surgery to place intracranial electrodes, we studied spike rate during long-term scalp EEG monitoring to further test this observation. METHODS We analyzed spike rate, seizure occurrence and AED taper in 130 consecutive patients over an average of 8.9days (range 5-17days). RESULTS We observed a significant relationship between time to the first seizure, spike rate, AED taper and seizure occurrence (F (3,126)=19.77, p<0.0001). A high spike rate was related to a longer time to the first seizure. Further, in a subset of 79 patients who experienced seizures on or after day 4 of monitoring, spike rate decreased initially from an on- to off-AEDs epoch (from 505.0 to 382.3 spikes per hour, p<0.00001), and increased thereafter with the occurrence of seizures. CONCLUSIONS There is an interplay between seizures, spikes and AEDs such that spike rate decreases with AED taper and increases after seizure occurrence. SIGNIFICANCE The direct relationship between spike rate and AEDs and between spike rate and time to the first seizure suggests that spikes are a marker of inhibition rather than excitation.

Localization of the ictal onset zone with MEG using minimum norm estimate of a narrow band at seizure onset versus standard single current dipole modeling.

Literature on the yield of ictal magnetoencephalography (MEG) is limited to case reports and a few case series (Assaf et al., 2003; Eliashiv et al., 2002; Mohamed et al., 2007; Tang et al., 2003; Tilz et al., 2002; Yagyu et al., 2010). Most of these studies were done using single Equivalent Current Dipole (sECD) model in order to localize seizure onset zone. There are some conceptual challenges when it comes to implementing this model in localization of ictal rhythms, especially in cases of paroxysmal fast activity. Successful sECD-fitting rate appears to decrease as a function of frequency as studied by de Jongh et al. (2003). In this report, we describe a new method of analysis of ictal rhythms and implement it in an illustrative case. Although both approaches yielded concordant results at the lobar level, the rhythm-based approach provided more accurate sublobar localization. Successful surgical resection, guided by intracranial EEG, contained the area of activation delineated by the rhythm-based method leaving behind the sECD area.

Yield of repeat routine MEG recordings in clinical practice

From 377 consecutive MEG studies for patients with intractable epilepsy performed at the Cleveland Clinic between 2008 and 2011, 19 patients were referred for a repeat MEG. Source localization was done using a single equivalent current dipole (ECD) model on identified interictal spike activity. Clinical, neuroimaging, and concurrent EEG and MEG findings were reviewed. The most common reasons for repeating MEG were as follows: negative initial study in 6 patients, paucity of recorded interictal discharges in 4, failed surgeries in 3, uncertain findings in the first study in 2, and research-related reasons in 4. Repeat MEG provided new localizing findings in 11/19 patients (58%), of whom 6 had negative or rare interictal findings in the first study. Lobar concordance of dipoles was present in 6 (85%) of the 7 patients with positive findings in both MEG studies. This study demonstrates that a repeat MEG may provide new localization data when a previous recording shows limited or no interictal abnormalities.

Presurgical language fMRI: Technical practices in epilepsy surgical planning

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, image acquisition, analysis and interpretation, and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or 5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in routine use with forms of noun–verb generation, verbal fluency, and semantic decision‐making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best‐validated protocols was used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language‐related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, and brain–behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best‐validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.