Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.

BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. MATERIALS AND METHODS: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. RESULTS: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. CONCLUSIONS: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.

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.

Epileptic focus localization based on resting state interictal MEG recordings is feasible irrespective of the presence or absence of spikes.

OBJECTIVE: To investigate whether epileptogenic focus localization is possible based on resting state connectivity analysis of magnetoencephalographic (MEG) data. METHODS: A multivariate autoregressive (MVAR) model was constructed using the sensor space data and was projected to the source space using lead field and inverse matrix. The generalized partial directed coherence was estimated from the MVAR model in the source space. The dipole with the maximum information inflow was hypothesized to be within the epileptogenic focus. RESULTS: Applying the focus localization algorithm (FLA) to the interictal MEG recordings from five patients with neocortical epilepsy, who underwent presurgical evaluation for the identification of epileptogenic focus, we were able to correctly localize the focus, on the basis of maximum interictal information inflow in the presence or absence of interictal epileptic spikes in the data, with three out of five patients undergoing resective surgery and being seizure free since. CONCLUSION: Our preliminary results suggest that accurate localization of the epileptogenic focus may be accomplished using noninvasive spontaneous "resting-state" recordings of relatively brief duration and without the need to capture definite interictal and/or ictal abnormalities. SIGNIFICANCE: Epileptogenic focus localization is possible through connectivity analysis of resting state MEG data irrespective of the presence/absence of spikes.

Voxel-based morphometric MRI post-processing in MRI-negative focal cortical dysplasia followed by simultaneously recorded MEG and stereo-EEG.

We aim to report on the usefulness of a voxel-based morphometric MRI post-processing technique in detecting subtle epileptogenic structural lesions. The MRI post-processing technique was implemented in a morphometric analysis program (MAP), in a 30-year-old male with pharmacoresistant focal epilepsy and negative MRI. MAP gray-white matter junction file facilitated the identification of a suspicious structural lesion in the right frontal opercular area. The electrophysiological data by simultaneously recorded stereo-EEG and MEG confirmed the epileptogenicity of the underlying subtle structural abnormality. The patient underwent a limited right frontal opercular resection, which completely included the area detected by MAP. Surgical pathology revealed focal cortical dysplasia (FCD) type IIb. Postoperatively the patient has been seizure-free for 2 years. This study demonstrates that MAP has promise in increasing the diagnostic yield of MRI reading in challenging patients with "non-lesional" MRIs. The clinical relevance and epileptogenicity of MAP abnormalities in patients with epilepsy have not been investigated systematically; therefore it is important to confirm their pertinence by performing electrophysiological recordings. When confirmed to be epileptogenic, such MAP abnormalities may reflect an underlying subtle cortical dysplasia whose complete resection can lead to seizure-free outcome.

Circadian patterns of pediatric seizures.

OBJECTIVE: To evaluate the relationship of sleep/wake and day/night pattern to various seizure subtypes and epilepsy localizations. METHODS: Charts of 380 consecutive pediatric patients with epilepsy undergoing video-EEG (V-EEG) over 2 years were reviewed for seizure semiology, EEG localization, occurrence during the day (6 am-6 pm) or night, during wakefulness and sleep, 3-hour time blocks throughout 24 hours, and various epilepsy localizations, and etiology. RESULTS: A total of 1,008 seizures were analyzed in 225 children (mean age 8.5 ± 5.7 years). Sleep and wakefulness predicted seizure semiology and localization more reliably than daytime and nighttime. Auras, gelastic, dyscognitive, atonic, hypomotor, and myoclonic seizures, and epileptic spasms occurred more often in wakefulness, while tonic, tonic-clonic, automotor, and hypermotor seizures occurred more frequently in sleep (p < 0.05). Clonic, atonic, myoclonic, and hypomotor seizures occurred more frequently during daytime. Hypermotor and automotor seizures occurred more frequently at night (p < 0.05). Generalized seizures (6 am-12 pm), temporal lobe seizures (9 pm-9 am), frontal lobe seizures (12 am-6 am), parietal lobe seizures (6 am-9 am), and occipital lobe seizures (9 am-noon and 3-6 pm) revealed specific circadian patterns (p < 0.05). In addition, generalized and temporal lobe seizures occurred more frequently in wakefulness, while frontal and parietal seizures occurred more frequently in sleep, independent of day or night pattern (p < 0.05). CONCLUSION: Sleep and wakefulness, as well as time of day and night, are important considerations in proper characterization of seizure types and epilepsy localization. These findings may contribute to a better understanding of the mechanisms of nonrandom distribution of seizures, and may provide information for individualized treatment options.

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.

A self-administered screening instrument for psychogenic nonepileptic seizures.

BACKGROUND: Delay in distinguishing psychogenic nonepileptic seizures (PNES) from epilepsy may result in significant health and economic burdens. Screening tools are needed to facilitate earlier identification of patients with PNES, thereby maximizing cost-effective use of video electroencephalography (VEEG), the expensive gold standard for differentiating PNES from epilepsy. We developed and prospectively validated a self-administered PNES screening questionnaire using variables known to distinguish PNES from epilepsy patients. METHODS: Adults referred for inpatient VEEG monitoring at two epilepsy centers were prospectively invited to complete a preliminary 209-item questionnaire assessing demographic, clinical, seizure-related, and psychosocial information that appeared in the literature as potentially useful indicators of PNES. A hybrid neural-bayesian classifier was trained to predict PNES using a sample at one center, and was prospectively validated on a separate set of naive patients from both centers. RESULTS: Of 211 enrolled subjects from the training center, 181 met the study criteria for either PNES (n = 48, 27%), epilepsy (n = 116, 64%), or coexisting PNES and epilepsy (n = 17, 9%). Variable reduction procedures identified 53 questionnaire items that were necessary to accurately predict PNES diagnosis. The hybrid classifier predicted PNES diagnosis with 94% sensitivity and 83% specificity at the training center, and 85% sensitivity and 85% specificity at the second center (n = 46; 17 PNES, 26 epilepsy, 3 with coexisting PNES and epilepsy). CONCLUSIONS: We developed and prospectively validated a self-administered psychogenic nonepileptic seizure screening questionnaire that could hasten referral for video electroencephalography and reduce the health and economic burdens from delayed diagnosis or misdiagnosis.

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.

Electrical stimulation and gene-based neuromodulation for control of medically-refractory epilepsy.

The failure of available antiepileptic medications to adequately control seizures in a substantial number of patients underscores the need to develop novel epilepsy therapies. Recent advancements in technology and the success of neuromodulation in treating a variety of neurological disorders have spurred interest in exploring promising therapeutic alternatives, such as electrical stimulation and gene-based synaptic control. A variety of different stimulation approaches to seizure control targeting structures in the central or peripheral nervous system have been investigated. Most studies have been based on uncontrolled observations and empirical stimulation protocols. Today the vagus nerve stimulator is the only FDA approved adjunctive treatment for epilepsy that utilizes electrical stimulation. Other potential strategies including direct stimulation of the epileptogenic cortex and deep brain stimulation of various targets are currently under investigation. Chronically implanted devices for electrical stimulation have a variety of limitations. First, they are susceptible to malfunction and infection. Second, most systems require battery replacement. Finally, electrical stimulation is incapable of manipulating neuronal function in a transmitter specific fashion. Gene delivery to epileptogenic targets or targets implicated in regulating seizure threshold has been investigated as an alternative means of neuromodulation in animal models. In summary, positive preliminary results and the lack of alternative treatment options provide the impetus for further exploration of electrical stimulation and gene-based therapies in pharmacoresistant epilepsy. Various specific targets and approaches to modulating their activity have been investigated in human studies.