Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series.

BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.

Lateralisation of non-metric rhythm.

There are contradictory results on lateralisation and localisation of rhythm processing. Our aim was to test whether there is a hemispheric dissociation of metric and non-metric rhythm processing. We created a non-metric rhythm stimulus without a sense of metre and we measured brain activities during passive rhythm perception. A total of 11 healthy, right-handed, native female Hungarian speakers aged 21.3 ± 1.1 were investigated by functional magnetic resonance imaging (fMRI) using a 3T MR scanner. The experimental acoustic stimulus consisted of comprehensive sentences transformed to Morse code, which represent a non-metric rhythm with irregular perceptual accent structure. Activations were found in the right hemisphere, in the posterior parts of the right-sided superior and middle temporal gyri and temporal pole as well as in the orbital part of the right inferior frontal gyrus. Additional activation appeared in the left-sided superior temporal region. Our study suggests that non-metric rhythm with irregular perceptual accents structure is confined to the right hemisphere. Furthermore, a right-lateralised fronto-temporal network extracts the continuously altering temporal structure of the non-metric rhythm.

[Clinical application of functional MRI for chronic epilepsy]. / Klinischer Einsatz der funktionellen MRT bei chronischer Epilepsie.

Functional magnetic resonance imaging (fMRI) is frequently used in the presurgical diagnostic procedure of epilepsy patients, in particular for lateralization of speech and memory and for localization of the primary motor cortex to delineate the epileptogenic lesion from eloquent brain areas. fMRI is one of the non-invasive procedures in the presurgical diagnostic process, together with medical history, seizure semiology, neurological examination, interictal and ictal EEG, structural MRI, video EEG monitoring and neuropsychology. This diagnostic sequence leads either to the decision for or against elective epilepsy surgery or to the decision to proceed with invasive diagnostic techniques (Wada test, intra-operative or extra-operative cortical stimulation). It is difficult to evaluate the contribution of the fMRI test in isolation to the validity of the entire diagnostic sequence. Complications such as memory loss and aphasia in temporal lobe resections or paresis after frontal lobe resections are rare and rarely of disastrous extent. This further complicates the evaluation of the clinical relevance of fMRI as a predictive tool. In this article studies which investigated the concordance between fMRI and other diagnostic gold standards will be presented as well as the association between presurgical fMRI and postsurgical morbidity.

Long-term outcome of lesional posterior cortical epilepsy surgery in adults.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term seizure outcome and to find predictors of outcome after epilepsy surgery in lesional posterior cortical epilepsies (PCEs). METHODS: The operative outcome in 80 consecutive adult patients with lesional PCEs who underwent resective surgery for intractable partial epilepsy between 1991 and 2006 was retrospectively studied. RESULTS: The probability of remaining in Engel Class I was 66.3% (95% CI 60 to 72) at 6 months, 52.5% (95% CI 47 to 57) at 2 years, 52.9% (CI 45 to 59) at 5 years and 47.1% (CI 42 to 52) at 10 years. Factors predicting poor outcome were the presence of a somatosensory aura, extraregional spikes, incomplete resection, interictal epileptiform discharge (IED) in EEG 6 months and 2 years postsurgery, history of generalised tonic-clonic seizure (GT-CS) and the presence of focal cortical dysplasia in the resected specimen. Factors predicting good outcome were childhood onset of epilepsy, short epilepsy duration, ipsilateral spikes, visual aura, presence of well-circumscribed lesion in preoperative MRI and a pathologically defined tumour. In the multivariate analysis, predictors were different in the long and short term as follows: incomplete resection as proven by postoperative MRI (hazard ratio (HR) 2.059 (CI 1.19 to 3.67)) predicts seizure relapse in short-term follow-up. The presence of IED in the EEG performed 6 months after surgery (HR 2.3 (CI 1.128 to 4.734)) predicts seizure relapse in the long-term fellow-up. However, the absence of a history of GT-CS independently predicts seizure remission in short- and long-term follow-up. CONCLUSIONS: Surgery in PCEs proved to be effective in short- and long-term follow-up. Lesional posterior cortical epilepsy may be a progressive process in a substantial number of cases.

Very long-term outcome in resected and non-resected patients with temporal lobe epilepsy with medial temporal lobe sclerosis: A multiple case-study.

PURPOSE: To investigate the very long-term (i.e., ≥15 years) seizure, cognitive and psycho-social outcomes in resected patients (RP) with TLE compared to control patients not having undergone epilepsy surgery. METHODS: We applied a multiple case-study design including three non-resected patients (NRP) who were compared to a group of six RP. The latter were matched to the NRP according to clinical-demographic data. Outcome measures were various seizure, cognitive, and psycho-social variables. RESULTS: Patients were 56-72 years old. Seizure and AED outcome was more favourable among RP. RP reported better self-perceived overall health but higher subjective memory complaints. Upon formal neuropsychological testing, RP presented with lower verbal memory scores. Very long-term memory decline was evident in left-sided RP with good baseline memory scores, while RP with lower baseline performance, right-sided RP and NRP remained stable. Seizure-freedom had remarkable effects on the relationship between objective and subjective outcome: seizure-free patients, in general, subjectively reported the best psychosocial and cognitive outcome - irrespective of neuropsychological test results. CONCLUSION: Our study suggests positive effects of TLE surgery in the very long-term course of ≥15 years postoperatively. Long-term seizure-freedom appears to have the strongest impact on patients' subjectively perceived psycho-social and cognitive outcome and may even outweigh actual memory disturbances and/or decline. Overall, our data do not support the assumption of a generally accelerated cognitive decline in patients with TLE.

The contribution of 18F-FDG PET in preoperative epilepsy surgery evaluation for patients with temporal lobe epilepsy A meta-analysis.

OBJECTIVE: To assess the predictive diagnostic added value of positron emission tomography (PET) in preoperative epilepsy surgery evaluation for patients with temporal lobe epilepsy (TLE). METHODS: A meta-analysis of publications from 1992 to 2006 was performed. Forty-six studies were identified that met inclusion criteria presenting detailed diagnostic test results and a classified postoperative outcome. Studies exclusively reporting on patients with brain tumors or on children were excluded. RESULTS: The analyses were complicated by significant differences in study design and often by lack of precise patient data. Ipsilateral PET hypometabolism showed a predictive value of 86% for good outcome. The predictive value was 80% in patients with normal MRI and 72% in patients with non-localized ictal scalp EEG. In a selected population of 153 TLE patients with a follow-up of >12 months PET correlated well with other non-invasive diagnostic tests, but none of the odds ratios of any test combination was significant. CONCLUSION: Our data confirm that ipsilateral PET hypometabolism may be an indicator for good postoperative outcome in presurgical evaluation of drug-resistant TLE, although the actual diagnostic added value remained questionable and unclear. PET does not appear to add value in patients localized by ictal scalp EEG and MRI. Prospective studies limited to non-localized ictal scalp EEG or MRI-negative patients are required for validation.

The role of 1H magnetic resonance spectroscopy in pre-operative evaluation for epilepsy surgery. A meta-analysis.

PURPOSE: We aimed to assess the additional pre-operative value of (1)H MRS in identifying the epileptogenic zone (EZ) for epilepsy surgery by performing a meta-analysis considering publications from 1992 to 2003. METHODS: From an extensive computer and hand search 22 studies were included. For inclusion, studies had to report post-operative outcome and detailed diagnostic test results for each individual patient. Studies exclusively reporting on patients with brain tumors or on children were excluded. RESULTS: Great heterogeneity among studies regarding methodological and technical aspects and concerning evaluation and interpretation of data was observed. Only patients with intractable temporal lobe epilepsy were presented. Sixty-four percent of all patients and 72% of patients with good outcome had an ipsilateral MRS abnormality concordant with the EZ. The positive predictive value of all patients with ipsilateral MRS abnormality for good outcome was 82%. An odds ratio weighted by inverse variance showed a 4.891 better chance of seizure free outcome [CI=1.965-12.172; Q=2.748; d.f.=5; critical chi2-value=11.07] in patients with an ipsilateral MRS abnormality when compared to patients with bilateral MRS abnormalities. Data for MRI-negative patients were conflicting. One study stressed a role for MRS in patients with bilateral hippocampal atrophy at MRI. CONCLUSIONS: MRS still remains a research tool with clinical potential. Our findings indicate the connection of ipsilateral MRS abnormality to good outcome. The ability for prediction of post-operative outcome may depend on the assessed population. Prospective studies limited to non-localized ictal scalp EEG or MRI-negative patients are required for validation of these data.

Amygdala enlargement in dysthymia--a volumetric study of patients with temporal lobe epilepsy.

BACKGROUND: Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS: There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS: This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.

Memory fMRI lateralizes temporal lobe epilepsy.

BACKGROUND: The assessment of mesial temporal lobe (MTL) function is important for the diagnosis and treatment of temporal lobe epilepsy (TLE) and other brain diseases. Declarative memory depends on the integrity of the MTL region. OBJECTIVE: To investigate hemispheric asymmetries of MTL activity in patients with symptomatic TLE. METHODS: With use of blood oxygenation level-dependent fMRI, hemispheric asymmetries in MTL activation of 30 individual patients with refractory symptomatic TLE and 17 healthy control subjects were studied. Activation was induced by a task employing mental navigation and recall of landmarks based on the retrieval of individually familiar visuospatial knowledge. RESULTS: The study demonstrated that the memory task used reliably activated MTL structures in individual control subjects and patients with refractory TLE including children, older subjects, and patients with low formal IQ. Interhemispheric differences in MTL activation lateralized the side of seizure onset in 90% of patients with symptomatic unilateral TLE. In contrast, healthy control subjects did not show a systematic asymmetry of MTL activation. Correlations between MTL activation and neuropsychological measures suggest that the fMRI-detectable MTL changes were specifically related to memory rather than to memory-independent visuospatial abilities. CONCLUSION: fMRI of memory-induced MTL activation lateralizes the side of seizure onset in patients with refractory symptomatic TLE and may provide complementary information for presurgical evaluation.

11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI.

BACKGROUND: Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE). OBJECTIVE: To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI. METHODS: Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis. RESULTS: Significant abnormalities of absolute FMZ-Vd were found after partial volume effect correction in 5 of 10 patients: unilateral decrease in the amygdala ipsilateral to the EEG focus (1), unilateral hippocampal decreases and bilateral temporal and extratemporal neocortical decreases (2), unilateral increase in the temporal neocortex together with extratemporal neocortical increases (1), and bilateral posterior hippocampal increases together with temporal neocortical increases (1). In the three patients with extratemporal neocortical changes, the concomitant unilateral hippocampal or temporal neocortical changes were contralateral to the presumed epileptic focus. Significant asymmetries of FMZ-Vd between homologous regions were found in six patients. In four of those patients, absolute FMZ-Vd for the homologous regions were within normal limits, with two of the four patients showing relatively higher hippocampal values ipsilateral to the presumed epileptic focus. SPM analysis localized significant abnormalities of FMZ-Vd in similar locations in three of the seven patients in whom VOI analysis detected significant changes. In addition, SPM indicated significant unilateral contralateral hippocampal decreases in an eighth patient. However, both methods failed to localize epileptic foci in two patients identified by depth-EEG recordings. CONCLUSIONS: 11C-FMZ PET showed focal increases as well as decreases of FMZ binding in 80% of patients with refractory TLE and normal high-quality MRI but was not consistently helpful in localizing the epileptic foci.

Measurement of temporal lobe T2 relaxation times using a routine diagnostic MR imaging protocol in epilepsy.

OBJECTIVE: To determine the applicability of a fast spin-echo (FSE) pulse sequence for T2 relaxation time measurements in diagnostic imaging of temporal lobe epilepsy (TLE) and in epilepsy research. To compare FSE T2-relaxometry to the measurements with multi-echo sequence and visual assessment of MR scans. METHODS: MR imaging and T2 relaxometry was performed with widely used 1.5 T scanner only. Fast dual-echo sequence (TE-14/85 ms) and multi-echo pulse sequence were used for T2 measurements. Normal ranges of T2 values in regions of interest in temporal lobe were estimated in 20 healthy controls. Sixty-five patients with intractable focal epilepsy were studied. Fifty-five patients had TLE, three multilobar focal epilepsy and seven extratemporal focal epilepsy. RESULTS: T2 measurements with the FSE showed good reproducibility in the test objects and control subjects. In one TLE case unilateral focal T2 changes were not identified visually. T2-relaxometry was more sensitive than visual inspection of MR scans in assessing bilateral hippocampal changes: there were 15 cases with abnormal bilateral T2 values. Visually bilateral changes were detected in six out of these 15 cases (40%). In six cases (40%) only unilateral changes were diagnosed visually, and in three cases (20%) bilateral changes were classified as probable with qualitative evaluation. T2 relaxation time measurement supplied additional objective data in cases with ambiguous hippocampal changes on visual assessment: T2-relaxometry confirmed hippocampal abnormalities in seven cases judged visually as probable. In four cases with the suspicion of hippocampal changes T2 values appeared to be normal. CONCLUSION: In TLE patients, images constructed from FSE sequences can be used to estimate T2 relaxation times easily and reliably. T2 measurements are an objective method to diagnose structural changes in the temporal lobe. T2-relaxometry is most helpful to assess bilateral hippocampal abnormalities, and thus might have an impact on estimating postsurgical outcome.

Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study.

BACKGROUND AND PURPOSE: It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry) influences the blood oxygenation level dependent (BOLD) contrast changes induced by neuronal activation and measured by functional MRI (fMRI). We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE). MATERIAL AND METHODS: Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL) activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. RESULTS: In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P < 0.001). Activation over the supposedly normal MTL, i.e. contralateral to the seizure onset of TLE patients, was smaller than the averaged MTL activation in healthy controls (P < 0.005). Age, duration of epilepsy, side of seizure onset, and intelligence were not correlated to the extent of the significant BOLD-response over both MTL in patients with TLE. CONCLUSIONS: In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

Reproducible localization of interictal epileptiform discharges using EEG-triggered fMRI.

We report preliminary experiences using fMRI triggered by EEG to localize the site of interictal epileptiform activity. EEG was recorded in the scanner and monitored on-line; the recording quality was good enough to allow the clear identification of spikes in the EEG. Snap-shot EPI was performed 2-4 s after an epileptiform discharge ('spike') or after at least 10 s of background activity ('rest') was observed. A pixel-by-pixel t-test was performed between the 'rest' and the 'spike' images to determine areas of significant activation. Significant activation was obtained in a patient with epilepsy. To assess the reliability and reproducibility of the technique, the patient was scanned on four separate occasions with similar areas being activated in all the studies, confirming the validity of the result.

One-year functional magnetic resonance imaging follow-up study of neural activation during the recall of unresolved negative life events in borderline personality disorder.

BACKGROUND: Recall of adverse life events under brain imaging conditions has been shown to coincide with activation of limbic and prefrontal brain areas in borderline personality disorder (BPD). We investigate changes of functional magnetic resonance imaging (fMRI) activation patterns during the recall of unresolved adverse life events (ULE) over 1 year. METHOD: Thirteen female BPD patients participated in the study. During fMRI measurement subjects recalled ULE and negative but resolved life events (RLE) after individual cue words to stimulate autobiographical memory retrieval. Subjective intensity of emotional and sensoric experiences during recall was assessed as well as standardized measures of psychopathology. RESULTS: A 2x2 factorial analysis of fMRI data (Deltat1/t2xDeltaULE/RLE) revealed major right more than left differences of activation (i.e. t1>t2) of the posterior more than anterior cingulate, superior temporal lobes, insula, and right middle and superior frontal lobes (second-level analysis, t=3.0, puncorrected=0.003). The opposite contrast (Deltat2/t1xDeltaULE/RLE) did not reveal any differences. We did not find changes of emotional or sensoric qualities during recall (ULE versus RLE) or of psychopathology measures over the 1-year period. CONCLUSIONS: Although subjective and clinical data did not change within 1 year, we observed a substantial decrease of temporo-frontal activation during the recall of ULE from t1 to t2. If future research confirms these findings, the question arises whether the decrease of neural activation precedes clinical improvement in BPD.

Amygdala fMRI lateralizes temporal lobe epilepsy.

OBJECTIVE: To characterize the clinical value of an fMRI task activating the amygdala in controls and patients with mesial temporal lobe epilepsy (MTLE). METHODS: A fearful face fMRI paradigm using video sequences was developed and investigated in 17 patients with epilepsy (12 had MTLE [6 right- and 6 left-sided]) and 17 healthy control subjects. Reproducibility was demonstrated by reimaging 12 of the control subjects. In addition, parahippocampal activation was measured using Roland's Hometown Walking Task within the same session in all patients and in nine of the control subjects. RESULTS: A fearful face paradigm led to significant amygdala activation (p < 0.001) in all subjects. Amygdala activation was bilateral in control subjects and clearly lateralized in patients with MTLE. Dissociated amygdala and parahippocampal activation was found in three MTLE patients. A combination of results from both fMRI paradigms improved the lateralization of the side of seizure onset in patients with MTLE. CONCLUSIONS: fMRI activation of the amygdala evoked by an animated fearful face paradigm is strong, reproducible, and specific in individual subjects. The combination of the fearful face paradigm and Roland's Hometown Walking Task provides a more reliable presurgical mapping of mesial temporal lobe structures.

Transient lesion in the splenium of the corpus callosum and antiepileptic drug withdrawal.

OBJECTIVE: To test pathophysiologic hypotheses regarding the occurrence of a splenial lesion in patients with epilepsy. METHODS: The authors studied 16 patients with a splenial lesion and 32 control patients, all of whom had MRI examination immediately after presurgical EEG long-term monitoring (LTM). The authors compared the number of generalized tonic-clonic and partial seizures during LTM, antiepileptic drug (AED) withdrawal, and laboratory results. RESULTS: All of the patients with a splenial lesion had their AEDs stopped completely, vs 47% of the controls (p = 0.001). Patients with SCC lesion had a longer duration of complete withdrawal (median 3.5 vs 2 days, p = 0.03). There was no correlation with seizure frequency or the introduction of new AEDs. CONCLUSION: A lesion of the splenium of the corpus callosum in patients with epilepsy is not associated with toxic drug effects or high seizure frequency, but might be induced by a rapid and relatively long-lasting reduction of antiepileptic drugs. Its frequency might be underestimated as MRI after long-term monitoring is rarely done.

Cavernous angioma associated with ipsilateral hippocampal sclerosis.

We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA.

Multiple pterygium syndrome, bilateral periventricular nodular heterotopia and epileptic seizures--a syndrome?

We present the clinical, neurophysiological and radiographic findings in a boy with coexisting multiple pterygium syndrome, bilateral periventricular nodular heterotopia (BPNH), mental retardation and epileptic seizures. This constellation has not been previously reported. We discuss the possibility of a new BPNH syndrome associated with multiple pterygium syndrome in our patient.

Fast, accurate, and reproducible automatic segmentation of the brain in T1-weighted volume MRI data.

A new fast automated algorithm has been developed to segment the brain from T1-weighted volume MR images. The algorithm uses automated thresholding and morphological operations. It is fully three-dimensional and therefore independent of scan orientation. The validity and the performance of the algorithm were evaluated by comparing the automatically calculated brain volume with semi-automated measurements in 10 subjects, by calculating the brain volume from repeated scans in another 10 subjects, and by visual inspection. The mean and standard deviation of the difference between semi-automated and automated measurements were 0.56% and 2.8% of the mean brain volume, respectively, which is within inter-observer variability of the semi-automated method. The mean and standard deviation of the difference between the total volumes calculated from repeated scans were 0.40% and 1.2% of the mean brain volume, respectively. Good results were also obtained from a scan of abnormal brains.

Voxel-by-voxel comparison of automatically segmented cerebral gray matter--A rater-independent comparison of structural MRI in patients with epilepsy.

Quantitative evaluation of MRI in patients with epilepsy can give more information than qualitative assessment. Previously developed volume-of-interest-based methods identified subtle widespread structural changes in the neocortex beyond the visualized lesions in patients with malformations of cortical development (MCD) and hippocampal sclerosis (HS) and also in MRI-negative patients with juvenile myoclonic epilepsy (JME). This study evaluates a voxel-based automated analysis of structural MRI in epilepsy. After fully automated segmentation of cerebral gray matter from structural T1-weighted, high-resolution MRI scans, we applied the automated and objective technique of statistical parametric mapping (SPM) to the analysis of gray matter of 35 control subjects, 10 patients with partial seizures and MCD, 10 patients with left temporal lobe epilepsy (TLE) and HS, 10 patients with left TLE and normal MR quantitation of the hippocampus, and 20 patients with JME. At a corrected threshold of P < 0.05, significant abnormalities were found in 3/35 controls; in all 10 patients with MCD, 6 of whom had additional lesions beyond the margins of the visualized abnormalities; in 2/10 TLE patients with HS; in 2/10 MRI-negative TLE; and in 4/20 JME patients. Group comparisons between control subjects and HS patients identified the affected left temporal lobe with an increase in gray matter in the posterior temporal lobe, but did not identify hippocampal atrophy. The group of MRI-negative TLE patients showed no abnormalities compared with control subjects. Group comparison between control subjects and JME patients identified a mesial frontal increase in gray matter. The SPM-based voxel-by-voxel comparison of gray matter distribution identified MCD and abnormalities beyond the visualized lesion in individual MCD patients. The method did not reliably identify HS in individual patients or identify abnormalities in individual MRI-negative patients with TLE or JME in a proportion larger than the chance findings in the control group. Using group comparisons, structural abnormalities in the neocortical gray matter of patients with TLE and HS were lateralized to the affected temporal lobe. In patients with JME as a group, an increase in gray matter was localized to the mesial frontal area, corroborating earlier quantitative MRI findings.