Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion-weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR-negative epilepsy patients.

Diagnosis of retrocochlear lesions with emphasis on expansion of the cerebellopontine angle.

The correct diagnosis of CPA tumours is a relatively common issue in both neurological and ENT practice, the omission of which can have serious consequences for the patient. Properly set clinical guidelines and diagnostic protocols are key aspects of good clinical practice. In the case of CPA tumours, two options are available: the first is diagnosis with the help of an ABR as the primary tool for determining the group of patients with a possible tumour; the second is an MRI scan of the posterior cranial fossa. With an appropriately set diagnostic protocol in place, and despite the 40% chance of failure of the ABR to detect tumours less than or equal to 1 cm, similar treatment results can be achieved with much higher cost efficacy in case of primary ABR testing.

Atypical handedness in mesial temporal lobe epilepsy.

OBJECTIVE: The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population. METHODS: Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated. RESULTS: We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p=0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8years of age [median; min-max 0.5-17] in left-handers versus 15years of age [median; min-max 3-30] in right-handers (p<0.001). CONCLUSIONS: Left-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.

Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy.

OBJECTIVE: The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG). METHODS: According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology. RESULTS: Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found. CONCLUSIONS: According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.

Long-term outcome and predictors of resective surgery prognosis in patients with refractory extratemporal epilepsy.

PURPOSE: We analyzed the long-term postoperative outcome and possible predictive factors of the outcome in surgically treated patients with refractory extratemporal epilepsy. METHODS: We retrospectively analyzed 73 patients who had undergone resective surgery at the Epilepsy Center Brno between 1995 and 2010 and who had reached at least 1 year outcome after the surgery. The average age at surgery was 28.3±11.4 years. Magnetic resonance imaging (MRI) did not reveal any lesion in 24 patients (32.9%). Surgical outcome was assessed annually using Engel's modified classification until 5 years after surgery and at the latest follow-up visit. RESULTS: Following the surgery, Engel Class I outcome was found in 52.1% of patients after 1 year, in 55.0% after 5 years, and in 50.7% at the last follow-up visit (average 6.15±3.84 years). Of the patients who reached the 5-year follow-up visit (average of the last follow-up 9.23 years), 37.5% were classified as Engel IA at each follow-up visit. Tumorous etiology and lesions seen in preoperative MRI were associated with significantly better outcome (p=0.035; p<0.01). Postoperatively, 9.6% patients had permanent neurological deficits. CONCLUSION: Surgical treatment of refractory extratemporal epilepsy is an effective procedure. The presence of a visible MRI-detected lesion and tumorous etiology is associated with significantly better outcome than the absence of MRI-detected lesion or other etiology.

Comparing the effects of cortical resection and vagus nerve stimulation in patients with nonlesional extratemporal epilepsy.

The main purpose of this retrospective study was to compare the effects of resective surgery (RESgr-26 patients) and vagus nerve stimulation (VNSgr-35 patients) on seizure frequency (2 and 5years after surgery) in patients with nonlesional extratemporal epilepsy (NLexTLE). We analyzed hospital admission costs directly associated with epilepsy (HACE) in both groups at the same follow-up. The decrease in seizure frequency from the preoperative levels, in both VNSgr and RESgr, was statistically significant (p<0.001). The seizure frequency reduction did not differ significantly between the follow-up visits for either group (p=0.221 at 2years and 0.218 at 5years). A significantly higher number of Engel I and Engel I+II patients were found in RESgr than in VNSgr at both follow-up visits (p=0.04 and 0.007, respectively). Using McHugh classification, we did not find statistically significant differences between both groups at both follow-up visits. Hospital admission costs directly associated with epilepsy/patient/year in both RESgr and VNSgr dropped significantly at 2- and 5-year follow-up visit and this reduction was not statistically different between RESgr and VNSgr (p=0.232). Both VNS and resective surgery cause comparably significant seizure reduction in NLexTLE. Resective surgery leads to a greater number of patients with excellent postoperative outcome (Engel I+II). The HACE reduction is statistically comparable between both groups.

Grey-white matter abnormalities in temporal lobe epilepsy associated with hippocampal sclerosis: Inter-observer analysis, histopathological findings, and correlation with clinical variables.

This study was conducted to determine the incidence of grey-white matter abnormalities (GWMAs) on magnetic resonance images (MRIs) in patients with hippocampal sclerosis (HS), to assess the inter-observer reliability of this finding, and to establish a possible relationship between GWMA and histopathological findings in the anterior part of the temporal lobe, as well as its other relation to clinical variables. We established a group of 55 patients with histologically proven HS. Three observers independently reviewed the MRIs to assess whether GWMA was present. Substantial independent inter-observer agreement was reached for 44 of the 55 patients (80%) (Fleiss' kappa 0.732; p<0.0001). GWMAs were present in 38% of patients (HS+GWMA). Focal cortical dysplasia (FCD) of type IIIa (ILAE classification) was present in 31% of patients. FCD type IIIa was present in 52.4% with HS+GWMA, and in 17.6% without GWMA (HS-GWMA) (p=0.007). We did not find any statistically significant differences in the postoperative outcomes between HS+GWMA and HS-GWMA. We did not find any statistically significant differences in the presence or absence of GWMA and FCD of the temporal pole in relation to the onset of epilepsy, the duration of epilepsy, or the presence of potential epileptogenic insults. GWMA in the anterior part of temporal lobe in patients with HS is a reliable assessment sign for observers who are experienced in evaluating the MRIs of epilepsy patients. The presence of GWMA is significantly associated with the presence of FCD type IIIa in these patients. The presence or absence of GWMA and FCD type IIIa does not influence the postoperative outcome of HS patients.

"MRI-negative PET-positive" temporal lobe epilepsy: invasive EEG findings, histopathology, and postoperative outcomes.

The aim of this retrospective study was to analyze invasive EEG findings, histopathology, and postoperative outcomes in patients with MRI-negative, PET-positive temporal lobe epilepsy (TLE) (MRI-/PET+TLE) who had undergone epilepsy surgery. We identified 20 patients with MRI-/PET+TLE (8.4% of all patients with TLE who had undergone surgery; 11 men, 9 women). Of the 20 patients, 16 underwent invasive EEG. The temporal pole and hippocampus were involved in the seizure onset zone in 62.5% of the patients. We did not identify a lateral temporal or extratemporal seizure onset in any patient. Of the 20 patients, 17 had follow-up periods >1 year (mean follow-up=3.3 years). At the final follow-up, 70.6% patients were classified as Engel I, 5.8% of patients as Engel II, and 11.8% of patients as Engel III and IV (11.8%). Histopathological evaluation showed no structural pathology in any resected hippocampus in 58% of all evaluated temporal poles. The most common pathology of the temporal pole was focal cortical dysplasia type IA or IB. MRI-/PET+TLE should be delineated from other "nonlesional TLE." The ictal onset in these patients was in each case in the temporal pole or hippocampus, rather than in the lateral temporal neocortex. Standard surgery produced a good postoperative outcome, comparable to that for patients with lesional TLE. Histopathological findings were limited: the most common pathology was focal cortical dysplasia type I.

fMRI evaluation of hemispheric language dominance using various methods of laterality index calculation.

Several functional MR imaging studies evaluating the lateralisation of linguistic functions in patients who underwent Wada testing have been reported. There is extensive variance in the Laterality index (LI) calculation across the studies, and the optimal calculation method remains unclear. We attempted to calculate the LI in different ways in the same subjects, in order to find the LI calculation method with the highest correlation to the Wada test. Fifteen patients (10 females, 5 males) suffering from medically intractable temporal lobe epilepsy (TLE) (12 left, 3 right) were admitted for the study. The patients underwent a standardized bilateral intracarotid short-acting barbiturate test. Language testing included spontaneous speech, oral comprehension, reading, object and picture naming, and repetition. All the tasks were scored separately in order to increase the possibility of correlation between Wada and LI. A silent phonemic verbal fluency task (VFT) was used as a language paradigm for functional measurement. Regions of interest (ROIs), with a known association with language function (Broca's area, the lateral prefrontal cortex, etc.), were defined. First, the LIs were calculated from the ROIs using a previously reported method (simple suprathreshold count). Next, we used several new methods of LI calculation (t-weighting of voxels, methods independent of the choice of the statistical threshold, etc.) The most significant correlation with Wada was proven in the LIs that were evaluated from Broca's area (up to R = 0.94, P = 1 x 10(-7)). However, the new LI calculation methods used in the present study did not produce a statistically significant benefit in comparison to previously reported methods.

Combining advanced neuroimaging techniques in presurgical workup of non-lesional intractable epilepsy.

PURPOSE: The rationale for this case report is to assess the degree of congruency between the results of several advanced functional, metabolic, and structural neuroimaging techniques used in patients with MRI-negative focal epilepsy. METHODS: We investigated the presurgical evaluation and post-operative outcome of a patient with intractable, extratemporal epilepsy. Because the habitual seizures in this patient could be easily induced, six, advanced, neurodiagnostic techniques were successively applied (SISCOM, ictal FDG-PET, ictal fMRI, postictal diffusion-weighted imaging, voxel-based morphometry, and MRS imaging). RESULTS: The findings for the neuroimaging methods investigated, within the left central region, were fairly congruent. Subsequent, invasive EEG recordings revealed a seizure-onset zone at the site where most of the neuroimaging had shown abnormal findings. The surgical removal of the epileptogenic zone, as defined by concordant neuroimaging and SEEG data, resulted in seizure-free postoperative outcome. Histopathological findings revealed mild focal cortical dysplasia. CONCLUSION: Great efforts should be made to combine most of the advanced neuroimaging methods in the preoperative assessment of non-lesional epilepsy surgery candidates.

Dropped head syndrome in severe intractable epilepsies with mental retardation.

PURPOSE: Dropped head syndrome is characterized by a gradual forward sagging of the head due to the isolated weakness of the neck extensor muscles. The syndrome has a relatively benign clinical course. To date, there have been no reports of dropped head syndrome in epileptic patients. METHODS: Nine patients with intractable epilepsy (mean age, 33.6+/-9.91 years), each presenting with apparent dropped head, were evaluated. The duration of the drooping head symptom varied from 3 to 15 years (mean, 7.4+/-4.06 years), with a slowly progressing weakness in most of the patients. In all of the patients, extensive clinical, laboratory, electrophysiological, histopathological, and neuroimaging examinations were performed. RESULTS: The weakness in all of the subjects was strictly limited to the cervical paraspinal muscles. Laboratory studies produced normal results from all subjects. EMG and muscle biopsy were normal or revealed subtle nonspecific myopathic changes without inflammation in the cervical paraspinal muscles. Polymyographic investigation revealed that none of the patients had convincing dystonic spasms of the anterior neck muscles. No atrophy or fatty changes of the neck extensor muscles were observed on CT or MRI. In most of the patients (7/9), altered L-carnitine concentrations were observed (four patients displayed a marked decrease in plasma carnitine concentrations, and three other patients showed abnormalities in urinary excretion of carnitine). CONCLUSIONS: These findings seem to suggest that a secondary carnitine deficiency, induced by antiepileptic drugs (principally valproic acid), represents a plausible pathogenetic mechanism for the development of dropped head in some epileptic patients.

Combined event-related fMRI and intracerebral ERP study of an auditory oddball task.

Event-related fMRI (efMRI) has been repeatedly used to seek the neural sources of endogenous event-related potentials (ERP). However, significant discrepancies exist between the efMRI data and the results of previously published intracranial ERP studies of oddball task. To evaluate the capacity of efMRI to define the sources of the P3 component of ERP within the human brain, both efMRI and intracerebral ERP recordings were performed in eight patients with intractable epilepsy (five males and three females) during their preoperative invasive video-EEG monitoring. An identical auditory oddball task with frequent and target stimuli was completed in two sessions. A total of 606 intracerebral sites were electrophysiologically investigated by means of depth electrodes. In accordance with the finding of multiple intracerebral generators of P3 potential, the target stimuli evoked MRI signal increase in multiple brain regions. However, regions with evident hemodynamic and electrophysiological responses overlapped only partially. P3 generators were always found within hemodynamic-active sites, if these sites were investigated by means of depth electrodes. On the other hand, unequivocal local sources of P3 potential were apparently also located outside the regions with a significant hemodynamic response (typically in mesiotemporal regions). Both methods should thus be viewed as mutually complementary in investigations of the spatial distribution of cortical and subcortical activation during oddball task.

Handedness shift as a consequence of motor cortex reorganization after early functional impairment in left temporal lobe epilepsy--an fMRI case report.

The impact of epileptiform activity on the functional organization of various cortical regions is currently a widely discussed topic. Our patient, suffering from left-sided temporal lobe epilepsy with typical mesiotemporal sclerosis, had a remarkable history of a clear-cut handedness shift in early childhood. In this study, we considered the possibility of the functional reorganization of the motor cortex using functional MRI. The results reflect epileptiform activity as an important formative factor for motor cortex development in our patient.