Magnetoencephalography adds to the surgical evaluation process.

Summarizing the podium discussion at the AES 2009, strengths and limitations of magnetoencephalography (MEG) are discussed with regard to basic methodological and clinical aspects in routine screening and presurgical evaluation of patients with epilepsies. Current literature and example cases are used to illustrate MEG contribution to clinical decision making, specifically whether a patient with pharmacoresistant epilepsy can move forward to epilepsy surgery. The main conclusion is that the largest role of MEG, as presently performed in the clinical environment, is to increase the number of patients who can go on to surgery, while it should not be used to deny surgery to any patient.

Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy.

OBJECTIVE: To assess the efficacy and tolerability of adjunctive levetiracetam in patients with uncontrolled generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsies (IGE). METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults and children (4 to 65 years) with IGE experiencing >or=3 GTC seizures during the 8-week baseline period (4-week retrospective and 4-week prospective), despite receiving stable doses of one or two antiepileptic drugs (AEDs). Patients were randomized to levetiracetam (target dose 3,000 mg/day for adults; 60 mg/kg/day for children) or placebo and a 4-week titration period was followed by a 20-week evaluation period. RESULTS: Of 229 patients screened, 164 were randomized (levetiracetam, n = 80; placebo, n = 84). Levetiracetam produced a greater mean reduction in GTC seizure frequency per week over the treatment period (56.5%) than placebo (28.2%; p = 0.004). The percentage of patients who had >or=50% reduction of GTC seizure frequency per week (responders) during the treatment period was 72.2% for levetiracetam and 45.2% for placebo (p < 0.001; OR 3.28; 95% CI 1.68 to 6.38). During the first 2-week treatment 64.6% of patients on levetiracetam and 45.2% on placebo (p = 0.018) were classified as responders. During the evaluation period the percent of patients free of GTC seizures (34.2% vs 10.7%; p < 0.001) and all seizure types (24.1% vs 8.3%; p = 0.009) was greater for levetiracetam than placebo. Levetiracetam was well tolerated with 1.3% of patients discontinuing therapy due to adverse events vs 4.8% on placebo. CONCLUSION: Adjunctive levetiracetam is an effective and well-tolerated antiepileptic drug for treating generalized tonic-clonic seizures in patients with idiopathic generalized epilepsies.

Racial disparities in the use of surgical treatment for intractable temporal lobe epilepsy.

OBJECTIVE: To compare the use of surgical treatment for epilepsy among different ethnic and racial groups with surgically remediable temporal lobe epilepsy (TLE). METHODS: The authors used multiple logistic regression analysis to model the use of anterior temporal lobectomy in a cross-sectional study of video-EEG monitoring discharge data among residents of Alabama and surrounding states discharged from the University of Alabama at Birmingham Hospital between July 1998 and January 2003 with a primary diagnosis of TLE. RESULTS: Of 432 patients diagnosed with TLE, 130 had evidence of mesial temporal sclerosis on MRI studies. Seventy patients underwent surgery; African Americans were less likely than non-Hispanic whites to undergo surgical treatment (odds ratio, 0.3; 95% CI, 0.2 to 0.8). After potential demographic (age, education, and sex), socioeconomic, medical insurance coverage, and clinical confounders (bitemporal seizure onset) were controlled, African Americans had a 60% less chance to receive surgery than non-Hispanic whites. CONCLUSIONS: There are disparities in the use of surgical treatment for temporal lobe epilepsy. Race appears to be an influential factor related to such disparities.

Chronic temporal lobe epilepsy: spatial extent and degree of metabolic dysfunction studied with magnetic resonance spectroscopy (MRS).

INTRODUCTION: Proton magnetic resonance spectroscopy ((1)H MRS) has been proposed as a lateralizing method for the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). Studies have shown correlations between temporal lobe (TL) NAA and seizure frequency, and TL NAA/Cr and the duration of epilepsy in patients with TLE. This latter finding may suggest that progressive neuronal dysfunction may occur in both temporal lobes in patients with TLE, even when the seizures originate in only one temporal lobe. We analyzed our data in an attempt to find a possible correlation between extension of neuronal dysfunction based on NAA measures and duration of epilepsy. METHODS: We studied 45 consecutive patients with the diagnosis of TLE, who were referred for presurgical evaluation. Duration of epilepsy was defined as the interval between the age of seizure onset and the time of the MRS examination. All studies were performed in the inter-ictal state, prior to intracranial monitoring or resection. We performed two-tailed Pearson correlation analysis between ipsilateral NAA/Cr and extension of the abnormality (voxels involved) and the duration of the seizure disorder in years. RESULTS: The average duration of epilepsy in this group was 20 years. No significant correlation was found between duration of epilepsy and mean hippocampal NAA/Cr (r=-.131, p=.390); nor was a correlation found between duration of epilepsy in years or the extent of metabolic lesion (voxels involved) (r=-.264, p=.079). CONCLUSIONS: Hippocampal NAA/Cr does not correlate with duration of epilepsy in TLE. Our findings suggest that cross-sectional group measures of hippocampal neuronal function do not suggest damage progression.

Neurotoxicity following addition of intravenous valproate to lamotrigine therapy.

Reversible neurotoxic symptoms were observed in three adult patients with absence status epilepticus on lamotrigine (LTG) therapy after administration of an IV bolus followed by oral valproic acid (VPA). Neurotoxicity was likely related to elevated serum LTG levels, as improvement correlated with discontinuing or reducing LTG dosage.

Temporal lobectomy for epilepsy: recovery of the contralateral hippocampus measured by (1)H MRS.

(1)H MRS imaging was obtained from 10 patients with mesial temporal lobe epilepsy before and after surgery. After surgery, metabolic recovery in the contralateral hippocampus was detected. Preoperatively, reduced N-acetylaspartate (p < 0.04) increased after surgery nonsignificantly to equal control values. Cholines increased after surgery (p < 0.02) and creatine-phosphocreatine showed a trend to higher values. The results suggest that the contralateral hippocampus is affected by repeated seizure activity in the ipsilateral hippocampus, rather than presence of bilateral mesial temporal sclerosis.

In vivo hippocampal glucose metabolism in mesial temporal lobe epilepsy.

BACKGROUND: The appearance of decreased 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake in the mesial temporal region in temporal lobe epilepsy may simply reflect loss of gray matter due to hippocampal atrophy. Increased partial volume effects due to atrophic hippocampi may further increase appearance of hypometabolism. METHODS: The authors used a combination of MRI-PET coregistration, with MRI-based gray matter segmentation, and partial volume correction to improve the examination of hippocampal specific glucose uptake in FDG PET. The goal was to determine 1) if relative mesial temporal hypometabolism is an artifact of gray matter (hippocampal) atrophy, 2) whether hippocampal metabolism correlates with atrophy evaluated on MRI, and 3) if MRI-based partial volume correction influences measurement of hippocampal metabolic-volume relationships, including epilepsy lateralization. RESULTS: Findings showed that ipsilateral hippocampi of mesial temporal lobe epilepsy (MTLE) are relatively hypometabolic per unit of gray matter volume, and that hippocampal metabolism directly correlates with hippocampal volume. Specifically, partial volume corrected hippocampal metabolism correlated strongly (r = 0.613, p < 0.001) with hippocampal volume. Without partial volume correction, a weaker, but still significant, correlation was present (r = 0.482, p < 0.001). Degree of asymmetry was consistently greater and provided higher sensitivity of lateralization with partial volume vs non-partial volume corrected metabolic measurements. CONCLUSIONS: Although, decreased metabolism may occur in the absence of neuronal cell loss, hippocampal atrophy and presumed degree of neuronal cell loss appears to be a primary factor involved in the cause of decreased metabolism in epileptogenic hippocampi. Partial volume correction is recommended for optimal interpretation of hippocampal structure and function relationships.

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy.

BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss.

Temporal ictal electroencephalographic frequency correlates with hippocampal atrophy and sclerosis.

We studied 328 complex partial seizures (CPS) in 63 consecutive patients with temporal lobe epilepsy who underwent scalp electroencephalography/video monitoring, magnetic resonance imaging (MRI), and surgery. The initial ictal discharge (IID), defined as the first sustained electrical seizure pattern localized to the surgical site, was determined. If the IID was rhythmic waves, the median frequency was measured. To determine if IID frequency correlates with hippocampal atrophy (HA) or sclerosis (HS), hippocampal volume ratios (HVRs) were measured (n = 52) or assessed visually (n = 11) on MRI, and mesial temporal histopathology specimens (n = 22) were graded for HS. Sixteen patients (25%) had no or mild HA (HVR = 0.78-1.02), and 47 patients (75%) had moderate-to-marked unilateral (HVR = 0.33-0.76), or bilateral, HA. Theta frequency IIDs were significantly more commonly associated with moderate-to-marked HA than were delta IIDs. Theta frequency IIDs occurred in 19% of patients with mild or no HA, and 79% of patients with moderate-to-marked HA; delta IIDs occurred in 63% of patients with little to no HA, and 13% of those with moderate-to-marked HA. In addition, the median IID frequency inversely correlated with HVR and directly correlated with HS severity. In conclusion, faster frequency rhythmic IIDs during temporal lobe CPS correlate with greater degrees of ipsilateral HA on MRI, and higher grades of HS.

Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy.

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.

Magnetoencephalography in partial epilepsy: clinical yield and localization accuracy.

The goals of this study were to determine (1) the yield of magnetoencephalography (MEG) according to epilepsy type, (2) if MEG spike sources colocalize with focal epileptogenic pathology, and (3) if MEG can identify the epileptogenic zone when scalp ictal electroencephalogram (EEG) or magnetic resonance imaging (MRI) fail to localize it. Twenty-two patients with mesial temporal (10 patients), neocortical temporal (3 patients), and extratemporal lobe epilepsy (9 patients) were studied. A 37-channel biomagnetometer was used for simultaneously recording MEG with EEG. During the typical 2-3-hour MEG recording session, interictal epileptiform activity was observed in 16 of 22 patients. MEG localization yield was greater in patients with neocortical epilepsy (92%) than in those with mesial temporal lobe epilepsy (50%). In 5 of 6 patients with focal epileptogenic pathology, MEG spike sources were colocalized with the lesions. In 11 of 12 patients with nonlocalizing (ambiguous abnormalities or normal) MRI, MEG spike sources were localized in the region of the epileptogenic zone as ultimately defined by all clinical and EEG information (including intracranial EEG). In conclusion, MEG can reliably localize sources of spike discharges in patients with temporal and extratemporal lobe epilepsy. MEG sometimes provides noninvasive localization data that are not otherwise available with MRI or conventional scalp ictal EEG.

Hippocampal N-acetylaspartate in neocortical epilepsy and mesial temporal lobe epilepsy.

Previous magnetic resonance spectroscopy (MRS) studies have shown that N-acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.

Temporal lobe epilepsy: bilateral hippocampal metabolite changes revealed at proton MR spectroscopic imaging.

PURPOSE: To determine which proton magnetic resonance (MR) spectroscopic imaging measures are best for lateralizing the seizure focus in patients who have temporal lobe epilepsy with and in those without hippocampal atrophy on MR images, the extent of contralateral abnormalities, and whether there is a correlation between MR spectroscopic imaging findings and surgical outcome. MATERIALS AND METHODS: MR spectroscopic imaging was performed in 16 adult patients with temporal lobe epilepsy and unilateral electroencephalographic findings and in 16 adult control subjects. Eleven patients underwent surgery; all patients underwent MR imaging. RESULTS: Nine patients had hippocampal atrophy on MR images. An ipsilateral decrease in the N-acetylaspartate concentration or the ratio of N-acetylaspartate to the sum of creatine and choline (N-acetylaspartate/ [creatine + choline]) was found in all patients. Decreased contralateral N-acetylaspartate concentration, N-acetylaspartate/(creatine + choline), or N-acetylaspartate concentration and N-acetylaspartate/(creatine + choline) were detected in eight patients (50%), which suggests bilateral abnormalities not detected with MR imaging. In the five patients who underwent surgery and did not show hippocampal atrophy on MR images, successful and unsuccessful outcomes were correctly predicted with N-acetylaspartate concentration. CONCLUSION: Decreased N-acetylaspartate concentration is not due solely to hippocampal atrophy. Contralateral abnormalities are much more frequent than expected. MR spectroscopic imaging is valuable in the presurgical evaluation of epilepsy.