Z. Irene Wang

The pathology of magnetic-resonance-imaging-negative epilepsy

Patients with magnetic-resonance-imaging (MRI)-negative (or ‘nonlesional’) pharmacoresistant focal epilepsy are the most challenging group undergoing presurgical evaluation. Few large-scale studies have systematically reviewed the pathological substrates underlying MRI-negative epilepsies. In the current study, histopathological specimens were retrospectively reviewed from MRI-negative epilepsy patients (n=95, mean age=30 years, 50% female subjects). Focal cortical dysplasia cases were classified according to the International League Against Epilepsy (ILAE) and Palmini et al classifications. The most common pathologies found in this MRI-negative cohort included: focal cortical dysplasia (n=43, 45%), gliosis (n=21, 22%), hamartia+gliosis (n=12, 13%), and hippocampal sclerosis (n=9, 9%). The majority of focal cortical dysplasia were ILAE type I (n=37) or Palmini type I (n=39). Seven patients had no identifiable pathological abnormalities. The existence of positive pathology was not significantly associated with age or temporal/extratemporal resection. Follow-up data post surgery was available in 90 patients; 63 (70%) and 57 (63%) attained seizure freedom at 6 and 12 months, respectively. The finding of positive pathology was significantly associated with seizure-free outcome at 6 months (P=0.035), but not at 12 months. In subgroup analysis, the focal cortical dysplasia group was not significantly correlated with seizure-free outcome, as compared with the negative-pathology groups at either 6 or 12 months. Of note, the finding of hippocampal sclerosis had a significant positive correlation with seizure-free outcome when compared with the negative-pathology group (P=0.009 and 0.004 for 6- and 12-month outcome, respectively). Absence of a significant histopathology in the resected surgical specimen did not preclude seizure freedom. In conclusion, our study highlights the heterogeneity of epileptic pathologies in MRI-negative epilepsies, with focal cortical dysplasia being the most common finding. The existence of positive pathology in surgical specimen may be a good indication for short-term good seizure outcome. There is a small subset of cases in which no pathological abnormalities are identified.

Magnetic source imaging and ictal SPECT in MRI‐negative neocortical epilepsies: Additional value and comparison with intracranial EEG

Purpose:  To investigate the utility of magnetic source imaging (MSI) and ictal single photon emission computed tomography (SPECT), each compared with intracranial electroencephalography (EEG) (ICEEG), to localize the epileptogenic zone (EZ) and predict epilepsy surgery outcome in patients with nonlesional neocortical focal epilepsy.

Voxel-based morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative epilepsies.

In the presurgical workup of magnetic resonance imaging (MRI)‐negative (MRI− or “nonlesional”) pharmacoresistant focal epilepsy (PFE) patients, discovering a previously undetected lesion can drastically change the evaluation and likely improve surgical outcome. Our study utilizes a voxel‐based MRI postprocessing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle abnormalities in a consecutive cohort of MRI− surgical candidates.

Optimizing SPECT SISCOM analysis to localize seizure‐onset zone by using varying z scores

Subtraction ictal single photon emission computed tomography (SPECT) co‐registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure‐free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score.

Neuroimaging characteristics of MRI‐negative orbitofrontal epilepsy with focus on voxel‐based morphometric MRI postprocessing

The orbitofrontal (OF) region is one of the least explored regions of the cerebral cortex. There are few studies on patients with electrophysiologically and surgically confirmed OF epilepsy and a negative magnetic resonance imaging (MRI) study. We aimed to examine the neuroimaging characteristics of MRI‐negative OF epilepsy with the focus on a voxel‐based morphometric MRI postprocessing technique.

The correlation of magnetoencephalography to intracranial EEG in localizing the epileptogenic zone: A study of the surgical resection outcome

OBJECTIVES To evaluate the agreement between magnetoencephalography (MEG) and intracranial electroencephalography (ICEEG) results, to determine the characteristics that lead to concordance, and to assess how these factors relate to favorable epilepsy surgery outcome. MATERIALS This retrospective study reviewed 50 patients who had positive MEG findings and ICEEG recordings between 2008 and 2010. The anatomical concordance between MEG and ICEEG recordings, the features of the MEG focus, and the relationship between the MEG focus and the surgically resected regions were correlated with the epilepsy surgery outcome. RESULTS Thirty-six of the 50 patients with positive MEG and ICEEG findings underwent epilepsy surgery, and 27 (75%) of the patients had an anatomical concordance of MEG/ICEEG. Among the patients with concordant MEG/ICEEG, the seizure free outcome rate was significantly higher compared to the discordant group [18/27 (66.7%) patients concordant vs. 1/9 (11.1%) patients discordant (p<0.006)]. Nineteen (53%) of the 36 patients had complete resection when the MEG focus overlapped with the resection area, and 15 (79%) of these 19 patients became seizure-free following surgery (p<0.001); 17 (47%) of the 36 patients had an MEG focus that was not completely resected (the MEG foci of 7 patients partially overlapped the resection areas, and 10 patients had MEG foci that were in a different area from the resection area), and 13/17 (76.5%) patients had seizure recurrences (p<0.001). CONCLUSIONS Both the anatomical concordance of MEG/ICEEG and the complete resection of the MEG foci significantly increased the chance of seizure-free outcomes following epilepsy surgery.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient’s other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Natural course and predictors of spontaneous seizure remission in idiopathic generalized epilepsy: 7–27 years of follow-up

The spontaneous course of idiopathic generalized epilepsy (IGE) is still controversial. The aim of this study was both to investigate the long-term spontaneous course and to identify factors that are predictive for epilepsy remission in a small cohort of 15 IGE patients (9 women) who refused antiepileptic drug (AED) treatment and therefore never have been treated with AED. All of them were reevaluated with a review of their medical records and direct face-to-face interview; the mean duration of follow-up was 15.3 years. Five (33.3%) of them had absence epilepsy (absence seizures, ABS), 5 had IGE with generalized tonic-clonic seizures (GTCS), and another 5 had both seizure types (IGE with ABS/GTCS). Rate of epilepsy remission was 53.3% with a mean time of seizure freedom of 13.1 years; rate of remission was highest among absence epilepsy patients (80%), followed by IGE with GTCS (60%) and IGE with ABS/GTCS (20%). The frequency of spontaneous generalized interictal epileptiform discharges in electroencephalography is not associated with the long-term seizure outcome (p=0.201) and per se does not require AED treatment. Furthermore, the occurrence of photoparoxysmal responses (p=0.020) as well as the occurrence of more than 3 GTCS during the course (p=0.029) were identified as significant predictors for a poor long-term seizure outcome which makes AED treatment indispensable in these patients. This study underlines the heterogenity of the group of IGE. AED treatment has no impact on the spontaneous course of IGE with ABS and/or GTCS. Several predictors for the long-term seizure outcome in patients with IGE were identified in this study.

Interconnections in superior temporal cortex revealed by musicogenic seizure propagation

Musicogenic epilepsy (ME) is an intriguing epilepsy syndrome with estimated prevalence of 1 per million [1]. Seizures are precipitated by complex and usually highly specific stimuli. ME has been the topic of several excellent reviews [2, 3], but reports of comprehensively studied patients are scarce [1]. Notably, ME can provide insights in auditory processing and seizure-triggering mechanisms in humans. We present here a patient with non-lesional ME, whose seizure initiation and propagation shed light on interconnections within the superior temporal cortex. A 42-year-old right-handed professional composer started having seizures at 11 years. Seizures became difficult-to-control after he entered music school. Stereotyped auras were consistently triggered by songs with familiar melody and lyrics. ‘‘Happy Birthday’’ and songs by Elton John were especially provocative, whereas jazz/instrumentals had no effect. Auras consisted of buzzing or muffled sounds several times/week, evolving into dialeptic seizures with staring, unresponsiveness, and postictal dysphasia once/month. Interictal scalp-EEG showed intermittent left temporal slowing without epileptiform abnormalities. Ictal EEG localized to the left temporal region. High-resolution MRI was normal. Subtraction ictal SPECT showed discrete area of hyperperfusion within the left lateral superior temporal gyrus (STG) and contiguous supratemporal plane (Fig. 1a). Interictal FDG-PET showed small but congruent area of decreased fluoro-deoxy-glucose uptake (Fig. 1b). To further delineate the epileptogenic zone and its relationship to eloquent cortex, we performed invasive evaluation with subdural grids covering left lateral temporal and perisylvian cortex, and depth electrodes targeting Heschl’s, planum temporale and mesial temporal structures (Fig. 1c). This unique patient was also evaluated with simultaneous intracranial-EEG and MEG sampled at 1,000 Hz. For standard analysis intracranial-EEG and MEG were band-passed with low-frequency cutoff of 5 Hz, and highfrequency cutoff of 70 and 50 Hz, respectively. No epileptic spikes were found interictally on either modality. We then provoked an ictal event in the MEG suite by having the patient listen to ‘‘Happy Birthday’’ followed by his favorite Elton John song. Two minutes later he reported typical aura of muffled sound. Discrete onset (Fig. 2, red arrow) was then seen in the LPST depth electrode contacts located within planum temporale (red contacts in Fig. 1c, left), represented by sharply contoured rhythmic theta evolving into repetitive spiking with overriding paroxysmal fast activity. Similar activities (Fig. 2, blue arrow) were observed on adjacent LST depth electrode in Heschl’s gyrus (blue contacts in Fig. 1c, left) starting 1.5 s later (first propagation site). These activities Z. I. Wang Y. Kakisaka R. C. Burgess J. A. Gonzalez-Martinez S. Ito J. C. Mosher S. Hantus A. V. Alexopoulos (&) Cleveland Clinic Epilepsy Center, 9500 Euclid Avenue, Desk S-51, Cleveland, OH 44195, USA e-mail: alexopa@ccf.org

Quantitative positron emission tomography-guided magnetic resonance imaging postprocessing in magnetic resonance imaging-negative epilepsies.

Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD.