Hippocampal Sclerosis Detection with NeuroQuant Compared with Neuroradiologists.

BACKGROUND AND PURPOSE: NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis. MATERIALS AND METHODS: We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology (n = 61) or not having hippocampal sclerosis on pathology (n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem. RESULTS: NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P < .001). The positive predictive value of NeuroQuant analysis was comparable with visual MR imaging analysis (84.0% versus 89.1%), whereas the negative predictive value was not comparable (79.8% versus 95.0%). CONCLUSIONS: Visual MR imaging analysis by a neuroradiologist with expertise in epilepsy had a higher sensitivity than did NeuroQuant analysis, likely due to the inability of NeuroQuant to evaluate changes in hippocampal T2 signal or architecture. Given that there was no significant difference in specificity between NeuroQuant analysis and visual MR imaging analysis, NeuroQuant can be a valuable tool when the results are positive, particularly in centers that lack neuroradiologists with expertise in epilepsy, to help identify and refer candidates for temporal lobe epilepsy resection. In contrast, a negative test could justify a case referral for further evaluation to ensure that false-negatives are detected.

Voxel-based morphometric magnetic resonance imaging postprocessing in non-lesional pediatric epilepsy patients using pediatric normal databases.

BACKGROUND AND PURPOSE: Pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy and negative (non-lesional) magnetic resonance imaging (MRI) is particularly challenging. Focal cortical dysplasia (FCD), a frequent pathological substrate in such setting, may be subtle on MRI and evade detection. The aim of this study was to use voxel-based MRI postprocessing to improve the detection of subtle FCD in pediatric surgical candidates. METHODS: A consecutive cohort of pediatric patients undergoing pre-surgical evaluation with a negative MRI by visual analysis was included. MRI postprocessing was performed using a voxel-based morphometric analysis program (MAP) on T1-weighted volumetric MRI, with comparison to an age-specific normal pediatric database. The pertinence of MAP-positive areas was confirmed by surgical outcome and pathology. RESULTS: A total of 78 patients were included. Forty-four patients (56%) had positive MAP regions. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome compared with the no/partial resection group (P < 0.001). Patients with no/partial resection of the MAP-positive regions had worse seizure outcomes than the MAP-negative group (P = 0.002). The MAP-positive rate was 100%, 77%, 63% and 40% in the 3-5, 5-10, 10-15 and 15-21 year age groups, respectively. MAP-positive rates were 45% in patients with temporal resection and 63% in patients with extratemporal resection. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome in the extratemporal group (P = 0.001) but not in the temporal group (P = 0.070). CONCLUSION: Our data suggest the importance of using MRI postprocessing in the pre-surgical evaluation process of pediatric epilepsy patients with apparently normal MRI.

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.

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

PURPOSE: 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. METHODS: We included six patients with OF epilepsy, who met the following criteria: surgical resection of the OF lobe with/without adjacent cortex, seizure-free for ≥12 months, invasive video-electroencephalography (EEG) monitoring showing ictal onset from the OF area, and preoperative MRI regarded as negative. Patients were investigated in terms of their image postprocessing and functional neuroimaging characteristics, electroclinical characteristics obtained from noninvasive and invasive evaluations, and surgical pathology. MRI postprocessing on T1 -weighted high-resolution scans was implemented with a morphometric analysis program (MAP) in MATLAB. KEY FINDINGS: Single MAP+ abnormalities were found in four patients; three were in the OF region and one in the ipsilateral mesial frontal area. These abnormalities were included in the resection. One patient had bilateral MAP+ abnormalities in the OF region, with the ipsilateral one completely removed. The MAP+ foci were concordant with invasive electrophysiologic data in the majority of MAP+ patients (four of five). The localization value of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and ictal single-photon emission computed tomography (SPECT) is low in this cohort. Surgical pathology included focal cortical dysplasia, remote infarct, Rosenthal fiber formation and gliosis. SIGNIFICANCE: Our study highlights the importance of MRI postprocessing in the process of presurgical evaluation of patients with suspected orbitofrontal epilepsy and "normal" MRI. Using MAP, we were able to positively identify subtle focal abnormalities in the majority of the patients. MAP results need to be interpreted in the context of their electroclinical findings and can provide valuable targets in the process of planning invasive evaluation.

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy.

The objective of this retrospective study was to determine if dual pathology [DUAL - focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (Mage=36.5years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS=28; DUAL=35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group×time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion.

Diffusion tensor imaging in patients with focal epilepsy due to cortical dysplasia in the temporo-occipital region: electro-clinico-pathological correlations.

PURPOSE: Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (anisotropy, FA) of water diffusion. We explored the characteristics of pathology-proven cortical dysplasia (CD) in the posterior quadrant in a case series of three patients using DTI measures, to assess associated alterations in subcortical connectivity and correlate with in situ epileptogenicity, seizure propagation and functional outcome. METHODS: The FA maps were visually inspected by a Neuroradiologist blinded to clinical data and conventional MRI (PR) and tractography was performed to assess connectivity of the dysplastic cortex and correlate with seizure propagation on invasive EEG. RESULTS: Analysis of FA maps revealed reduced connectivity with reduced arborization and thinning of the fiber bundles between the subcortical WM and the dysplastic cortex in patients 1 and 2, confirmed on tractography. Fiber tracts reconstructed from regions underlying the ictal onset help explain ictal propagation patterns. In the two patients without preexisting visual field deficit, resections spared the optic radiation visible on the FA map. CONCLUSIONS: Diffusivity measures and visualization of tracts provide complementary information on white matter changes accompanying CD and may assist to explain ictal spread patterns. Careful correlation with measures of function will allow the assessment of the functional significance of various dysplastic lesions and may help to design resective strategies.

Subdural electrode analysis in focal cortical dysplasia: predictors of surgical outcome.

OBJECTIVE: Patients undergoing epilepsy surgery for focal cortical dysplasia (FCD) guided by subdural EEG generally have a poor surgical outcome. Our objective was to identify predictors of postoperative seizure recurrence in this patient cohort. METHODS: We retrospectively reviewed 48 consecutive surgeries guided by subdural electrode recordings between 1990 and 2004 in patients with a pathologic diagnosis of isolated FCD. Using survival analysis, we analyzed results of the noninvasive evaluation, MRI, subdural interictal and ictal EEG patterns, extent of resection, proximity to eloquent cortex, and postoperative EEG. RESULTS: After a median follow-up of 2.7 years, 45% of patients were completely seizure-free. Most seizures recurred in the first 6 months or between years 2 and 3 after surgery. On univariate analysis, seizure recurrence was associated with bilateral EEG abnormalities, multiple semiologic seizure types, and incomplete resection of the ictal onset zone. The absence of an MRI lesion did not affect outcome, nor did proximity to eloquent cortex. Interictal paroxysmal fast and runs of repetitive spikes correlated with the ictal onset zone, whereas isolated spikes did not. The 6-month EEG predicted ultimate surgical failure in patients seizure-free at that stage. An ictal spread pattern from the edge of the subdural grids was an independent predictor of seizure recurrence on multivariate analysis. CONCLUSIONS: We have identified specific predictive factors that may guide the surgical evaluation of patients with focal cortical dysplasia and intractable epilepsy requiring subdural EEG monitoring. Successful surgical results can be obtained utilizing subdural EEG in carefully selected patients.

Successful surgery for epilepsy due to early brain lesions despite generalized EEG findings.

OBJECTIVE: To understand the role of epilepsy surgery in children with generalized or bilateral findings on preoperative scalp EEG. METHODS: From our pediatric epilepsy surgery series, we identified 50 patients in whom 30 to 100% of preoperative epileptiform discharges (ictal, interictal, or both) were generalized or contralateral to the side of surgery. RESULTS: All patients had severe refractory epilepsy and an epileptogenic lesion on brain MRI. Ninety percent of the lesions were congenital, perinatal, or acquired during infancy, predominantly malformations of cortical development (44%) or cystic encephalomalacia (40%). Age at surgery was 0.2 to 24 (median 7.7) years. Surgeries were hemispherectomy (64%) or lobar or multilobar resection. At last follow-up (median 24.0 months), 72% of patients were seizure-free, 16% had marked improvement with only brief episodes of staring or tonic stiffening, and 12% were not improved. The rate of seizure-free outcome was not significantly associated with age at seizure onset or surgery, presence of hemiparesis or focal clinical features during seizures, type of lesion, or surgery type. Postoperative seizure-free rate did not differ from that in a comparison group of similar patients who matched the study group except for their high percentage (70 to 100%) of ipsilateral ictal and interictal epileptiform discharges on preoperative EEG. CONCLUSIONS: Epilepsy surgery may be successful for selected children and adolescents with a congenital or early-acquired brain lesion, despite abundant generalized or bilateral epileptiform discharges on EEG. The diffuse EEG expression may be due to an interaction between the early lesion and the developing brain.

ApoE-epsilon4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy.

OBJECTIVE: To investigate the relationship between the apolipoprotein (ApoE) epsilon4 allele and memory performance (verbal and nonverbal) in patients with medically intractable temporal lobe epilepsy (TLE) who underwent temporal lobectomy. METHODS: Presurgical and postsurgical memory performance was examined in 87 adult patients with TLE (epsilon4 = 22; non-epsilon4 = 65) to determine whether the expression of ApoE-epsilon4 may be associated with memory performance in this population and to examine how this relationship may be affected by duration of epilepsy. RESULTS: There was a significant interaction between ApoE-epsilon4 status and duration of epilepsy such that epsilon4 carriers with a long duration of epilepsy demonstrated the poorest memory performance on both verbal and nonverbal measures. This relationship was observed both before and after temporal lobectomy, with little change in test performance over time. CONCLUSIONS: The ApoE-epsilon4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy.

The value of interictal diffusion-weighted imaging in lateralizing temporal lobe epilepsy.

BACKGROUND: A subgroup of patients with nonlesional temporal lobe epilepsy (TLE) has no evidence of hippocampal sclerosis on standard temporal lobe protocol MRI. OBJECTIVE: To investigate whether interictal diffusion-weighted imaging adds lateralizing information in patients with TLE with and without lateralizing conventional MRI. METHODS: We studied 22 patients (9 right, 13 left TLE) who had undergone temporal lobectomy and 18 control subjects. We measured hippocampal volumes on high- resolution coronal magnetization-prepared rapid gradient echo scans. Apparent diffusion coefficients (ADCs) for the entire hippocampus and three arbitrarily defined areas of interest within the hippocampal head, body, and tail were measured from the coregistered ADC map. Pathology was reviewed and correlated with imaging findings. RESULTS: Fourteen of 22 patients had hippocampal atrophy on MRI (defined as volume asymmetry greater than 2 SDs compared with asymmetry in the control group). Overall, resected hippocampi (n = 22) were significantly smaller than contralateral hippocampi as well as ipsilateral hippocampi in controls. ADCs were significantly higher in resected hippocampi than contralateral hippocampi as well as ipsilateral hippocampi in controls. These differences were also observed within the three areas of interest. ADCs in the hippocampi contralateral to the epileptogenic zone (n = 22) were also higher than in ipsilateral hippocampi in controls. In the subgroup of eight patients with nonlateralizing conventional MRIs, ADCs of resected hippocampi were not significantly different compared with the contralateral side. Pathology in these patients revealed gliosis only without apparent neuron loss. CONCLUSION: Interictal apparent diffusion coefficients confirm lateralization in patients with hippocampal atrophy on standard temporal lobe protocol MRI. However, they do not provide lateralizing information in patients with nonlateralizing conventional MRI.

Predictors of outcome after temporal lobectomy for the treatment of intractable epilepsy.

To assess short- and long-term seizure freedom, the authors reviewed 371 patients who underwent anterior temporal lobectomy to treat pharmacoresistant epilepsy. The mean follow-up duration was 5.5 years (range 1 to 14.1 years). Fifty-three percent of patients were seizure free at 10 years. The authors identified multiple predictors of recurrence. Results of EEG performed 6 months postoperatively correlated with occurrence and severity of seizure recurrence, in addition to breakthrough seizures with discontinuation of antiepileptic drugs.

Postoperative seizures after extratemporal resections and hemispherectomy in pediatric epilepsy.

OBJECTIVES: To estimate frequency and risk factors for acute postoperative seizures (APOS) within the first week after extratemporal cortical resection (ETR) and hemispherectomy (HS) in children and to assess the predictive value of APOS on long-term seizure outcome in this group. METHODS: The authors conducted a retrospective analysis of children (< 18 years), who underwent ETR or HS for intractable epilepsy between 1995 and 2002. APOS features and seizure outcome after ETR or HS were obtained at 6, 12, and 24 months. Univariate logistic regression was used for risk factors of APOS and life table analysis and log rank tests for seizure outcome at 0 to 6, 6 to 12, and 12 to 24 months. RESULTS: Of 132 patients, 34 (26%) had APOS. APOS were more frequent after ETR (26/71) than HS (8/61) (p < 0.01). APOS, irrespective of their timing, number, semiology, or other perioperative complications, were an independent predictor of poor postoperative seizure outcome at 2 years (p < 0.001). The estimated odds of postoperative Engel class I outcome in the APOS vs non-APOS categories was 0.27 (73% less likely) for 0- to 6-month, 0.22 (78% less likely) for 6- to 12-month, and 0.13 (87% less likely) for the 12- to 24-month intervals. CONCLUSIONS: Acute postoperative seizures (APOS) occur in 26% children, and the risk is higher after extratemporal cortical resection than hemispherectomy. APOS predict a poor postoperative seizure outcome at 6, 12, and 24 months. This study is useful for counseling families after epilepsy surgery. It also suggests that APOS may not be discounted as "benign" in research studies that evaluate seizure outcomes after epilepsy surgery.

Identification of candidates for epilepsy surgery in patients with tuberous sclerosis.

The authors reviewed preoperative MRI and EEG findings in relation to postsurgical outcome in 17 patients with refractory epilepsy due to tuberous sclerosis complex (TSC). Resecting concordant MRI (main tuber) and EEG abnormalities offered seizure freedom (8/9, 89%; median follow-up 25 months) comparable to other focal etiologies. Patients with nonconcordant MRI and EEG findings did less well (3/8, 38%, seizure free; p = 0.027, OR = 13).

Seizure outcome after epilepsy surgery in patients with normal preoperative MRI.

OBJECTIVE: To determine outcome after epilepsy surgery in patients with normal preoperative magnetic resonance imaging (MRI). METHODS: 24 adult and paediatric patients with normal preoperative MRIs were studied. They underwent epilepsy surgery between 1994 and 2001 and had at least one year of follow up. RESULTS: At the most recent follow up, nine patients (37%) were seizure-free and 18 (75%) had at least a 90% reduction in seizure frequency with weekly or monthly seizures. Seizure freedom was not significantly different after resections in frontal (5/9) or temporal regions (4/13) (p = 0.24, Fisher's exact test), or among patients with or without localising features on EEG, PET, or ictal SPECT. Subdural grids, used in 15 of 24 patients, helped tailor resections but were not associated with differences in outcome. Histopathology showed cortical dysplasia in 10 patients (42%), non-specific findings in 13 (54%), and hippocampal sclerosis in one (4%). Cortical dysplasia was seen in seven patients with frontal resection (78%) and non-specific findings in nine (69%) with temporal resection. Seizure outcome did not differ on the basis of location of resection or histopathology. CONCLUSIONS: While these results were less favourable than expected for patients with focal epileptogenic lesions seen on MRI, they represented worthwhile improvement for this patient population with high preoperative seizure burden. In this highly selected group, no single test or combination of tests further predicted postoperative seizure outcome.

Resective surgery to treat refractory status epilepticus in children with focal epileptogenesis.

Prolonged high-dose suppressive therapy (HDST) is a mainstay in the management of refractory status epilepticus (RSE), albeit with high morbidity and mortality. The authors studied 10 patients who were carefully selected for epilepsy surgery after failing prolonged (>2 weeks) HDST. Status epilepticus was stopped acutely in all of them with no mortality and no substantial morbidity. At follow-up (median 7 months), 7 (70%) of 10 patients were seizure free, and 3 (30%) of 10 had significant improvement in their epilepsy.

Temporal lobe volumes in patients with hippocampal sclerosis with or without cortical dysplasia.

BACKGROUND: Recent MRI-based volume reconstruction studies in intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) suggested atrophy that extends to the adjacent neocortical areas. OBJECTIVE: To study the extent of temporal lobe volume (TLV) abnormalities in patients with pathologically confirmed HS (with or without cortical dysplasia [CD]) who underwent anterior temporal lobectomy for the treatment of drug-resistant TLE. METHODS: Fifty patients (right TLE: n = 24; left TLE: n = 26) were found to have HS (hippocampal cell loss of >30%). Associated neocortical CD was seen in 20 patients (43%). MRI-based TLVs and hippocampal and hemispheric volume reconstructions in all patients were compared between pathologic groups and with volumes acquired from 10 age-matched control subjects. RESULTS: TLVs ipsilateral to the epileptogenic zone in patients with TLE were smaller than TLVs in control subjects (p < 0.01). In patients with left TLE, TLVs ipsilateral to the epileptogenic zone were smaller than contralateral TLVs (left: 66.6 +/- 8.3 cm3, right: 74.9 +/- 10.0 cm3; p < 0.001). In patients with right TLE, there were no significant asymmetries. The contralateral TLVs (regardless of the side of surgery) were smaller in the HS + CD group than the HS group (HS + CD group: 74.9 +/- 8.6 cm3, HS group: 79.7 +/- 6.6 cm3; p < 0.05). Patients with HS + CD had a tendency to have less hippocampal atrophy and slightly smaller TLVs ipsilateral to the epileptogenic zone, accounting for significantly smaller TLV/hippocampal volume ratios compared with patients with HS alone. CONCLUSIONS: Drug-resistant TLE due to HS is associated with extrahippocampal temporal lobe atrophy. The presence of bilateral temporal lobe atrophy is suggestive of a more widespread (bilateral) temporal lobe involvement in patients with HS and CD.

Localising and lateralising value of ictal piloerection.

BACKGROUND: Piloerection is a rare clinical symptom described during seizures. Previous reports suggested that the temporal lobe is the ictal onset zone in many of these cases. One case series concluded that there is a predominant left hemispheric representation of ictal cold. The aim of this study is to evaluate the localising and lateralising value of pilomotor seizures. METHODS: Medical records of patients who underwent video electroencephalogram (EEG) monitoring at the Cleveland Clinic between 1994 and 2001 were reviewed for the presence of ictal piloerection. The clinical history, physical and neurological examination, video EEG data, neuroimaging data, cortical stimulation results, and postoperative follow ups were reviewed and used to define the epileptogenic zone. Additionally, all previously reported cases of ictal piloerection were reviewed. RESULTS: Fourteen patients with ictal piloerection were identified (0.4%). Twelve out of 14 patients had temporal lobe epilepsy. In seven patients (50%), the ictal onset was located in the left hemisphere. Four out of five patients with unilateral ictal piloerection had ipsilateral temporal lobe epilepsy as compared with the ipsilateral side of pilomotor response. Three patients became seizure free after left temporal lobectomy for at least 12 months of follow up. An ipsilateral left leg pilomotor response with simultaneously recorded after-discharges was elicited in one patient during direct cortical stimulation of the left parahippocampal gyrus. CONCLUSIONS: Ictal piloerection is a rare ictal manifestation that occurs predominantly in patients with temporal lobe epilepsy. Unilateral piloerection is most frequently associated with ipsilateral focal epilepsy. No hemispheric predominance was found in patients with bilateral ictal piloerection.

Aphasia after hemispherectomy in an adult with early onset epilepsy and hemiplegia.

A 55 year old left handed man with left hemisphere subcortical encephalomalacia, seizures, language impairment, and right hemiparesis from a motor vehicle accident at age five was evaluated for epilepsy surgery. The patient continued to speak and followed commands during a left intracarotid amobarbital test (IAT). Left functional hemispherectomy resulted in expressive aphasia. Based on postoperative outcome, language was bilateral. The injury after primary development of language function, the predominantly subcortical lesion, and the late timing of surgical intervention well past development and plasticity may have been factors in the emergence of postoperative aphasia.