Neurophysiology, Neuropsychology, and Epilepsy, in 2022: Hills We Have Climbed and Hills Ahead. Neurophysiology in epilepsy.

Since the discovery of the human electroencephalogram (EEG), neurophysiology techniques have become indispensable tools in our armamentarium to localize epileptic seizures. New signal analysis techniques and the prospects of artificial intelligence and big data will offer unprecedented opportunities to further advance the field in the near future, ultimately resulting in improved quality of life for many patients with drug-resistant epilepsy. This article summarizes selected presentations from Day 1 of the two-day symposium "Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead". Day 1 was dedicated to highlighting and honoring the work of Dr. Jean Gotman, a pioneer in EEG, intracranial EEG, simultaneous EEG/ functional magnetic resonance imaging, and signal analysis of epilepsy. The program focused on two main research directions of Dr. Gotman, and was dedicated to "High-frequency oscillations, a new biomarker of epilepsy" and "Probing the epileptic focus from inside and outside". All talks were presented by colleagues and former trainees of Dr. Gotman. The extended summaries provide an overview of historical and current work in the neurophysiology of epilepsy with emphasis on novel EEG biomarkers of epilepsy and source imaging and concluded with an outlook on the future of epilepsy research, and what is needed to bring the field to the next level.

[Seizure prediction: from myth to reality]. / Prédiction des crises d'épilepsie: du mythe à la réalité.

INTRODUCTION: Clinical, metabolic and electrophysiologic studies suggest the existence of a preictal state, a transition between the interictal state and seizure. STATE OF THE ART: Analysis of the intracranial EEG by mathematical methods shows changes of the brain dynamics several minutes before the occurrence of partial seizures. These modifications can be widespread and not restricted to the epileptogenic focus, which would explain why they can also be detected from scalp EEG. Several scenarios could underlie the preictal state: a progressive recruitment of neurons or a facilitating state with a high probability of seizure occurrence. Because of the high rate of false predictions, no satisfactory method for seizure prediction has been currently proposed. PERSPECTIVES: A European multicenter study (Evolving platform for improving living expectation of patients suffering from IctAl events [EPILEPSIAE]) is currently evaluating a combination of 44 methods applied for EEG and ECG analysis on long-term recordings obtained from a large multicenter database (www.epilepsiae.eu). CONCLUSION: Combining analyses of multi-level signals including intracranial EEG and microelectrodes, scalp EEG and in vitro electrophysiological studies of post-operative tissues should help clarify brain dynamics during the pre-ictal state.

Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study.

Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD patients may help to understand the role of the lesion in epileptogenesis and also determine the potential surgical target.

Value of ictal and interictal epileptiform discharges and high frequency oscillations for delineating the epileptogenic zone in patients with focal cortical dysplasia.

OBJECTIVES: There are different neurophysiological markers of the Epileptogenic Zone (EZ), but their sensitivity and specificity for the EZ is not known in Focal Cortical Dysplasia (FCD) patients. METHODS: We studied patients with FCD who underwent stereoelectroencephalography (SEEG) and surgery. We marked in the SEEG: (a) typical and atypical interictal epileptiform patterns, (b) ictal onset patterns, and (c) rates of ripples (80-250 Hz) and fast ripples (FRs) (>250 Hz). High frequency oscillations were marked automatically during one hour of deep sleep. Surgical outcome was defined as good (Engel I) or poor (Engel II-IV). We computed the sensitivity and, as a measure of specificity, the false positive rate to identify the EZ, and compared them across the different neurophysiological markers. RESULTS: We studied 21 patients, 19 with FCD II. Ictal and typical interictal pattern were the markers with highest sensitivity, while the atypical interictal pattern had the lowest. We found no significant difference in specificity among markers. However, there is a tendency that FRs had the lowest false positive rate. CONCLUSION: The typical interictal pattern has the highest sensitivity. The clinical use of FRs is limited by their low sensitivity. SIGNIFICANCE: We suggest to analyze the typical interictal pattern first. FRs should be analyzed in a second step. If, for instance, a focus with FRs and no typical interictal pattern is found, this area could be considered for resection.

High-frequency oscillations during human focal seizures.

Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.

Cortical and thalamic fMRI responses in partial epilepsy with focal and bilateral synchronous spikes.

OBJECTIVE: To determine the blood oxygen level-dependent (BOLD) responses to epileptic discharges in the thalamus and cerebral cortex in patients with partial epilepsy. METHODS: Among 64 tested patients, 40 had EEG spikes during scanning and were divided in two groups: unilateral or bilateral independent spikes (29 patients) and bilaterally synchronous spikes (11 patients). Each spike topography was analyzed separately, yielding 40 studies in the first group and 17 in the second. RESULTS: Forty-five percent of focal spike studies showed significant BOLD responses. Cortical activation (positive BOLD) represented the dominant response and had a better correlation with spike location than cortical deactivation (negative BOLD). In the second group, all patients had significant BOLD responses; they were more widespread compared to the first group, and deactivated areas were as important as activated regions. A thalamic response was seen in 12.5% of studies in the first group and 55% in the second. CONCLUSIONS: The thalamus is involved in partial epilepsy during interictal discharges. This involvement and also cortical deactivation are more commonly seen with bilateral spikes than focal discharges. SIGNIFICANCE: These findings show evidence for a role for the thalamus and a more important role for inhibition in secondary bilateral synchrony.

Is ictal recording mandatory in temporal lobe epilepsy? Not when the interictal electroencephalogram and hippocampal atrophy coincide.

OBJECTIVE: To investigate the concordance between scalp electroencephalogram (EEG) lateralization and side of hippocampal atrophy in patients with temporal lobe epilepsy (TLE). METHODS: We studied 184 consecutive patients with TLE without lesions other than those compatible with mesial temporal sclerosis. In this study, we studied specifically hippocampal atrophy and the results of scalp EEG investigation. Patients were classified according to the localization of interictal epileptiform discharges as unilateral, bilateral asymmetric, and bilateral symmetric. The EEG seizure onsets were also classified separately as unilateral, bilateral asymmetric, and bilateral symmetric. The hippocampal atrophy was determined by volumetric measurements using high-resolution magnetic resonance imaging (MRIVol). RESULTS: Only 3% of patients had discordance between the ictal and interictal EEG lateralizations; however, none of these had unilateral interictal EEG abnormalities. Interictal EEGs were considered unilateral in 62.0% of patients, bilateral asymmetric in 31.5%, and bilateral symmetric in 6.5%. Ictal EEGs were considered unilateral in 63.5% of patients, bilateral asymmetric in 30.0%, and bilateral symmetric in 6.5%. The MRIVol showed unilateral hippocampal atrophy in 60.9% of patients, bilateral asymmetric hippocampal atrophy in 19.0%, symmetric hippocampal atrophy in 3.8%, and normal volumes in 16.3%. There was a significant concordance between MRIVol lateralization and both interictal and ictal EEG lateralization (P<.001). All patients with unilateral hippocampal atrophy had concordant interictal and ictal EEG lateralization. Six (18.2%) of the 33 patients with bilateral asymmetric hippocampal atrophy had MRI lateralization discordant with EEG lateralization. CONCLUSIONS: We found a strong concordance between EEG and MRIVol lateralization in patients with TLE. Unilateral hippocampal atrophy predicted ipsilateral interictal epileptiform abnormalities and ipsilateral seizure onsets with no false lateralization. Previous studies in addition to the present series support that a concordant outpatient EEG evaluation in patients with TLE and unilateral hippocampal atrophy would obviate the need for inpatient EEG monitoring.

Specificity of volumetric magnetic resonance imaging in detecting hippocampal sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampal formation are useful in detecting unilateral hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. In this pathologic entity, volumetric MRI analysis shows the epileptogenic structure to be atrophic when compared with the normal, nonepileptogenic side. Some authors have suggested that the radiological features of atrophy of medial temporal lobe structures are common in patients with complex partial seizures, but also are seen frequently in other seizure types and can occur even in patients without epilepsy. OBJECTIVE: To determine if seizures originating in extrahippocampal sites cause gliosis, cell loss, and atrophy of medial temporal lobe structures (i.e., HS). METHODS: We studied 110 patients with chronic epilepsy using volumetric MRI measurements of the hippocampal formation. Seventeen patients had pathologically proven HS, 27 patients had seizures due to extratemporal structural lesions, 15 patients had seizures caused by extrahippocampal temporal lobe lesions, 29 patients had primary generalized epilepsy, and 22 patients had secondary generalized epilepsy. RESULTS: All 17 patients with HS showed significantly reduced absolute hippocampal formation volumes of greater than 2 SDs below the mean of the control groups. The preoperative hippocampal formation volume measurements correlated well with the severity of HS on pathological examination. Hippocampal volumes were within the normal range in all patients with primary generalized epilepsy, secondary generalized epilepsy, extratemporal structural lesions, and extrahippocampal temporal lobe lesions. CONCLUSIONS: Seizures originating at extrahippocampal sites do not cause gliosis, cell loss, or atrophy of medial temporal structures. Significant reduction in hippocampal volumes is a specific marker for HS.

Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy.

BACKGROUND: Piracetam has been proven to be effective and well tolerated in the treatment of myoclonus in short-term studies. OBJECTIVE: To assess its long-term clinical efficacy, 11 patients with disabling myoclonus due to progressive myoclonus epilepsy were treated with piracetam in an open-label study. METHODS: Neurologic outcome (at the 1st, 6th, 12th, and 18th month of treatment) was assessed by an adjusted sum score of the following 3 indices: motor impairment, functional disability, and global assessment of disability due to myoclonus. Severity of other neurologic symptoms (seizure frequency and severity, dysarthria, and gait ataxia) also was assessed. Treatment with piracetam was initiated at a dose of 3.2 g/d that was gradually increased until stable benefit was noted (maximal dose in the trial was 20 g/d). Concomitant antiepileptic drugs were maintained at their previous dose. RESULTS: Statistically significant improvement in the total rating score was observed after introduction of piracetam at the 1st, 6th, and 12th month of treatment. Severity of other neurologic symptom scores did not improve significantly. Two patients reported drowsiness during the first 2 weeks of treatment. CONCLUSIONS: Piracetam given as add-on therapy seems to be an effective, sustained, and well-tolerated treatment of myoclonus. In patients with progressive myoclonus epilepsy, the efficacy of the drug increased during the first 12 months of treatment and then stabilized.

Life-threatening focal status epilepticus due to occult cortical dysplasia.

OBJECTIVE: Neuronal migration disorders are usually, but not necessarily, demonstrated by magnetic resonance imaging. Preoperative suspicion of these anomalies in the presence of normal magnetic resonance studies has important practical implications. This study delineates some clinical features that permit early suspicion of focal cortical dysplasia localized in the central and precentral regions. DESIGN: In a retrospective case series, we studied the clinical presentation of four consecutive patients with normal preoperative magnetic resonance images in whom focal cortical dysplasia was found in the surgical specimen. SETTING: Patients were seen in three referral centers specializing in epilepsy surgery. PATIENTS: Four patients (three female), between the ages of 4 and 21 years, had intractable partial seizures leading to resective brain surgery. INTERVENTION: Three patients had corticectomies in the central (two patients) or frontal (one patient) regions. One underwent an en bloc resection of the central area after two unsuccessful corticectomies and cortical transection. RESULTS: Three patients presented with life-threatening focal motor status epilepticus necessitating intubation, and one had epilepsia partialis continua. All had had seizures previously, and the attacks progressed to intractability after 1 1/2 to 3 years. Surgery led to control of the seizures, but only two patients became seizure free (mean follow-up, 15.7 months). All but one developed a postoperative deficit, which eventually improved. CONCLUSIONS: Focal cortical dysplasia should be suspected when life-threatening focal motor status epilepticus or epilepsia partialis continua occur in children or young persons without another obvious cause. Normal magnetic resonance studies do not exclude neuronal migration disorders.

Lateralizing value of peri-ictal headache: A study of 100 patients with partial epilepsy.

To determine the lateralizing value of peri-ictal headache, the authors conducted a standardized interview of 100 patients with partial epilepsy, 60 with temporal lobe epilepsy (TLE) and 40 with extratemporal epilepsy (ETE). Peri-ictal headache occurred in 47 of 100 (47%) patients. Peri-ictal headache was more likely to be ipsilateral to the seizure onset in TLE (27 of 30 = 90%) than in ETE (two of 17 = 12%; p< 0.001). For both groups, peri-ictal headache usually conformed to the diagnostic criteria for common migraine (18 of 30 = 60% in TLE; 7 of 17 = 41% in ETE).

Late-onset drop attacks in temporal lobe epilepsy: a reevaluation of the concept of temporal lobe syncope.

We report the clinical, radiologic, and EEG features of six patients with temporal lobe drop attacks (TLDA), all of whom underwent temporal resection. Postoperative follow-up of at least 1 year was available in all. TLDA were never the first manifestation but followed the onset of epilepsy after a long delay ranging from 7 to 43 years (mean, 24.4 years). Seizures were of unilateral temporal origin. In one patient, stereo EEG recording of TLDA showed rapid spread of the ictal discharge away from the temporal lobe in less than 1 second. Postoperatively, three patients were seizure free; one has had no TLDA but experiences sporadic auras; another, despite a reduction of more than 50%, continues to have complex partial seizures and TLDA; and the sixth has had sporadic secondarily generalized seizures upon reduction of antiepileptic medication. In conclusion, drop attacks may occur in temporal lobe epilepsy, usually long after the onset of epilepsy. They lead to increased disability and suggest a rapid spread of the ictal discharge and possible involvement of the pontine reticular formation rather than the presence of bitemporal foci or an extratemporal origin.

Nocturnal temporal lobe epilepsy.

OBJECTIVE: To analyze clinical, electrophysiologic, and neuroradiologic characteristics and prognostic factors in a group of patients with temporal lobe epilepsy (TLE) and complex partial seizures (CPS) occurring exclusively or predominantly after they fall asleep or before they awaken. BACKGROUND: CPS arising during sleep are classically identified with frontal lobe epilepsy. TLE associated with seizures occurring only or predominantly during sleep (nocturnal TLE) is less common. METHODS: From a series of patients with refractory TLE studied between 1980 and 1996, the authors identified 26 patients (15 men) with nonlesional nocturnal TLE (mean age, 40 years). Clinical and laboratory characteristics of these individuals were studied and compared with a group of 72 age-matched, randomly selected patients with nonlesional TLE and predominantly diurnal seizures (diurnal TLE). RESULTS: Mean age at seizure onset was similar for both groups (16.3 versus 18.7 years). In the nocturnal TLE group, 2 of 26 patients had a positive family history of epilepsy, 18 reported an aura, 4 presented with CPS in clusters, 11 had unilateral and 15 bilateral temporal EEG abnormalities, and 14 of 21 studied had unilateral mesial temporal atrophy. None of these factors differed significantly in the two groups except for higher frequency of the following in the diurnal TLE group compared with the nocturnal TLE group: positive family history for epilepsy (33% versus 8%, p=0.01), estimated frequency of seizures (median, 14 versus 2 per month; p < 0.01), and presence of antecedent febrile convulsions (33% versus 11%, p=0.04). In the nocturnal TLE group, eight patients underwent surgical therapy and became seizure free (follow-up, > 12 months). Only two were seizure free on medication. CONCLUSIONS: Infrequent and nonclustered seizures, rare family history of epilepsy, and low prevalence of childhood febrile convulsions characterize nocturnal TLE. Within the TLEs, the nocturnal TLE form seems to have a better surgical prognosis.

Neuronal metabolic dysfunction in patients with cortical developmental malformations: a proton magnetic resonance spectroscopic imaging study.

Cortical developmental malformations are best diagnosed by MRI and are often the cause of refractory epilepsy. Little is known about the metabolic cell function on MR spectroscopy of these types of brain anomaly. We studied 23 patients with cortical developmental malformations and refractory epilepsy using proton MR spectroscopic imaging. Mean age was 28 years (range, 9 to 47 years). The lesions examined were focal cortical dysplasia (n = 5), heterotopia (four band, six periventricular, two subcortical), polymicrogyria (n = 3), tuberous sclerosis (n = 2), and polymicrogyria and periventricular nodular heterotopia (n = 1). We measured the relative signal intensity of N-acetylaspartate/creatine (NAA/Cr) in the lesion, in the perilesional region, and in the region remote from the visible lesion. The values were compared with those from similar brain regions of 25 normal control subjects. The mean NAA/Cr z score values for the 23 patients were as follows: lesion, -2.20 +/- 0.32 (mean +/- SE), n = 21; perilesional region, -1.01 +/- 0.38, n = 15; and distant region, -0.03 +/- 0.34, n = 18 (p < 0.0002). Despite the presence of a large number of neurons, heterotopia showed a relative decrease of NAA in some patients, suggesting that the neurons present were dysfunctional. The maximal NAA/Cr decrease, indicating metabolic dysfunction, colocalized to the structural malformation as defined by MRI and extended to normal-appearing regions adjacent to the visible lesion.

Late-onset temporal lobe epilepsy and dilatation of the hippocampal sulcus by an enlarged Virchow-Robin space.

MRI signal changes within the hippocampal sulcus have been attributed to a dilated Virchow-Robin space within that sulcus, but no clinical correlates have previously been described. We present a 64-year-old man who developed right temporal seizures. MRI revealed an unusually enlarged Virchow-Robin space within the hippocampus, suggesting space-occupying effect. Such an abnormality should be considered a possible etiology in patients with late-onset temporal lobe epilepsy.

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes.

OBJECTIVE: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. BACKGROUND: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. METHODS: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. RESULTS: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. CONCLUSION: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.

Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy. Evidence from proton MR spectroscopic imaging.

Surgery is a safe and effective treatment for patients with temporal lobe epilepsy (TLE) who do not respond adequately to anticonvulsant medication and in whom the seizure generator can be identified and safely removed. Proton MR spectroscopic imaging (MRSI) can image and quantify neuronal damage in patients with TLE based on reduced signals from N-acetylaspartate (NAA), a compound localized exclusively in neurons. We performed proton MRSI in patients with TLE before and after surgical treatment to determine whether NAA or other resonance intensities changed in the temporal lobes of patients with TLE after surgery, and whether these changes correlated with surgical outcome. N-acetylaspartate resonance intensity relative to creatine (NAA/Cr) was abnormally low preoperatively in at least one temporal lobe in all 14 patients examined. It was low ipsilaterally in the patients who became seizure free and bilaterally in those who did not. Postoperatively, it increased to the normal range on the side of surgery in all patients who became seizure free. In the one patient who became seizure free and who had low NAA/Cr in both temporal lobes before surgery, NAA/Cr values in the contralateral, unoperated temporal lobe also increased to the normal range. In contrast, NAA relative intensity ratios did not change in those patients who continued to have seizures after surgery. The creatine resonance intensity (Cr) in the temporal lobes was high, relative to the brainstem, in seven patients preoperatively. After surgery, the Cr remained high in two patients, both of whom continued to have seizures. We conclude that NAA (and Cr) abnormalities in TLE do not result solely from neuronal loss and gliosis but can be reversible after postsurgical control of seizures. This implies that the NAA and Cr abnormalities in patients with TLE, at least in part, are dynamic markers of both local and remote physiologic dysfunction associated with ongoing seizures.

Entorhinal cortex in temporal lobe epilepsy: a quantitative MRI study.

BACKGROUND: The entorhinal cortex (EC) is a distinct anatomic and functional region of the anterior parahippocampal gyrus, which plays a role in seizure generation and propagation in temporal lobe epilepsy (TLE). In tissue resected from TLE patients, cell loss in the EC has been described. OBJECTIVES: To develop a standardized protocol for identifying the anatomic boundaries of the EC using high-resolution MRI and to examine morphologic changes of the EC in TLE. METHODS: We performed T1-weighted MRIs in 20 patients (7 males) with TLE (mean age 34 years) and 18 normal controls (mean age 26 years). Eleven patients had a left and 9 a right epileptic focus as defined by history, video-EEG, and surgical outcome. The volumes of the EC, the hippocampus, and the amygdala were measured using a standardized MRI protocol. Analysis of variance (ANOVA) was used to examine the effect of seizure focus lateralization and hemisphere on these volumes. An asymmetry ratio [A (%) = 100 x (R-L)/(R+L)/2] was also compared between groups using ANOVA. RESULTS: In normal controls the volume of the right EC was 1,247 +/- 127 mm3 (mean +/- standard deviation), and that of the left EC was 1,215 +/- 135 mm3 (p > 0.05). We found a bilateral reduction in the volume of the EC in TLE patients compared with controls (p < 0.05). Examination of the asymmetry ratios showed that the reduction in volume of the EC was greater ipsilateral to the epileptic focus (p < 0.05). The volumes of the hippocampus and the amygdala were smaller on the side of the focus in TLE patients compared with controls (p < 0.05). CONCLUSIONS: With a standardized protocol for the quantitative assessment of the EC, patients with unilateral TLE show bilateral reduction in the volume of the EC. However, this reduction is more severe ipsilateral to the epileptic focus.

Medial temporal lobe neuronal damage in temporal and extratemporal lesional epilepsy.

OBJECTIVE: To assess the extent of medial temporal lobe (TL) abnormalities of the neuronal marker N-acetylaspartate (NAA) in TL and extra-TL lesional partial epilepsy, and to determine whether decreases in NAA are related to lesion location, to lesion pathology, or to the seizures themselves. METHODS: The authors studied 19 patients with intractable partial epilepsy and an isolated structural cerebral lesion (10 TL, 9 extra-TL; 10 cortical dysplasia [CD], 9 non-CD lesions). Proton MRS imaging was used to determine the average relative resonance intensity of NAA for the TL regions of the left and right hemispheres. Values less than two SDs below the mean of normal control subjects were considered abnormal. RESULTS: Fourteen patients (74%) had abnormally low NAA relative to creatine (NAA/Cr) in at least one TL. Three-way analysis of variance (ANOVA; lesion pathology, lesion location, side of NAA/Cr decrease) showed that ipsilateral NAA/Cr was lower than contralateral (p = 0. 04). Three-way ANOVA (lesion location, generalized tonic-clonic seizures, side of NAA/Cr decrease) showed that generalized tonic-clonic seizures were associated with lower TL NAA/Cr (p = 0. 02). Lesion location and pathology showed no main effect on the NAA-to-Cr ratio in either analysis (p > 0.05). Linear regression analyses between seizure duration and NAA/Cr decrease was not significant. CONCLUSION: The authors demonstrated abnormally low TL NAA/Cr in the majority of patients with structural cerebral lesions. This abnormality did not differ with lesion location or pathology. They propose that the altered function of neuronal networks by an isolated structural cerebral lesion results in remote "functional dual pathology."

Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study.

We performed MRI volumetric measurements of the amygdala (AM) and hippocampal formation (HF) in a group of 43 patients with temporal lobe epilepsy not controlled by optimal drug treatment. Fifteen patients (35%) had a history of prolonged febrile convulsions (PFC) in early childhood; 30 patients underwent surgery, and histopathology was available in twenty-four. The mean values of AM and HF volumes ipsilateral to the EEG focus were significantly smaller than those of normal controls. The volumetric measurements showed a more pronounced atrophy of the AM in patients with a history of PFC, although the HF volumes were also smaller in this group. Patients with a history of PFC had a higher proportion of more severe mesial temporal sclerosis (MTS) compared with those with no PFC. These findings confirm a correlation between early childhood PFC, the severity of atrophy of mesial structures, and MTS.