Diffuse form of dysembryoplastic neuroepithelial tumour: the histological and immunohistochemical features of a distinct entity showing transition to dysembryoplastic neuroepithelial tumour and ganglioglioma.

AIMS: A diffuse variant of dysembryoplastic neuroepithelial tumour (dDNT) has previously been described, which although composed of oligodendroglia-like cells (OLC), astrocytes and mature neurones, lacks the multinodularity and 'specific component' of typical DNT. The dDNT poses a significant challenge to the neuropathologist. This study was undertaken to further characterize the histological and immunohistochemical features of dDNT. MATERIALS AND METHODS: Review of our archived material from epilepsy surgery identified 16 cases, in which features of dDNT predominated. Their histological and immunohistochemical features, including CD34 and nestin immunohistochemistry, were analysed. RESULTS: Seven cases had the characteristics of pure dDNT. A further two cases of dDNT showed extension into the white matter with occasional dysplastic neurones. Two additional cases had similar features but with the presence of either single, or multiple small nodular clusters of OLC, in keeping with transition to classical DNT. Five cases showed ganglioglioma-like areas, of which three cases had micronodule formation but with predominant dDNT pattern. In all the cases the dDNT areas showed strong CD34 and less intense nestin immunoreactivity and microglial activation highlighting the full extent of the lesions. There was variable overlap between CD34 and nestin positivity within the micronodular and/or ganglioglioma-like areas. CONCLUSIONS: Immunoreactivity for CD34 and nestin characterizes the dDNT and helps to distinguish it from other lesions associated with epilepsy. Histological evidence indicative of transition of dDNT to other forms of DNT and ganglioglioma suggests that dDNT might be an early histogenetic form of these glioneuronal tumours.

Imaging haemodynamic changes related to seizures: comparison of EEG-based general linear model, independent component analysis of fMRI and intracranial EEG.

BACKGROUND: Simultaneous EEG-fMRI can reveal haemodynamic changes associated with epileptic activity which may contribute to understanding seizure onset and propagation. METHODS: Nine of 83 patients with focal epilepsy undergoing pre-surgical evaluation had seizures during EEG-fMRI and analysed using three approaches, two based on the general linear model (GLM) and one using independent component analysis (ICA): The results were compared with intracranial EEG. RESULTS: The canonical GLM analysis revealed significant BOLD signal changes associated with seizures on EEG in 7/9 patients, concordant with the seizure onset zone in 4/7. The Fourier GLM analysis revealed changes in BOLD signal corresponding with the results of the canonical analysis in two patients. ICA revealed components spatially concordant with the seizure onset zone in all patients (8/9 confirmed by intracranial EEG). CONCLUSION: Ictal EEG-fMRI visualises plausible seizure related haemodynamic changes. The GLM approach to analysing EEG-fMRI data reveals localised BOLD changes concordant with the ictal onset zone when scalp EEG reflects seizure onset. ICA provides additional information when scalp EEG does not accurately reflect seizures and may give insight into ictal haemodynamics.

Pregabalin as adjunctive therapy for partial epilepsy: an audit study in 96 patients from the South East of England.

INTRODUCTION: Pregabalin (PGB) was licensed in the EU in 2004 as an adjunctive therapy in partial epilepsy. It is also licensed for neuropathic pain and generalised anxiety. AIMS: To identify the clinical usefulness and side effects of add-on PGB in out-patient epilepsy clinics. METHODS: We performed an audit on 96 consecutive patients (44 male) prescribed PGB for refractory epilepsy. Mean follow-up, for those who remained on PGB, was 23 months (range 12-39 months). RESULTS: Fifty patients remained on PGB, 37 of whom reported clear improvement in seizure frequency. Among these 37 patients, 1 was seizure free for 15 months; 29 had a seizure reduction of >50%; and 7 improved by <50%. Eight patients reported a decrease in seizure severity without change in seizure frequency. Nine patients reported an incidental improvement in anxiety. Side effects were reported by 25 patients out of the 50 patients still on treatment: 12 reported drowsiness or tiredness, 8 weight gain, 7 dizziness, 2 headache, 2 cognitive side effects, 1 irritability, 1 itchiness, 1 anxiety, and 1 transient rash. Among the 46 patients who discontinued treatment, 9 had worsening of seizure frequency, 27 lack of efficacy and 9 intolerable side effects necessitating withdrawal (4 dizziness or drowsiness, 2 weight gain, 1 peripheral oedema, 1 pain in arms and legs, 1 irritability and cognitive side effects). One patient had a seizure related death (probably drowning) within 1 month of starting PGB. CONCLUSION: Pregabalin seems to be an effective and well-tolerated anti-epileptic drug when used as add-on treatment in patients with refractory partial epilepsy.

Misdiagnosis in epilepsy: a review and recognition of diagnostic uncertainty.

The diagnosis of first seizure or epilepsy may be challenging and misdiagnosis can occur. Studies carried out in various settings have reported misdiagnosis rates of between 4.6% and 30%. Misdiagnosis can lead to serious consequences including driving and employment restrictions and inappropriate treatments. Most studies focus on ways of reducing misdiagnosis. However, in some cases, it may be difficult to make a definite diagnosis at initial presentation. This is because of a number of reasons including overlapping clinical features with other conditions, inadequate available history and limitations of investigations. Consequently, diagnostic uncertainty is inevitable in epilepsy, although few studies acknowledge this. In this paper we review the literature on misdiagnosis rates, analyse reasons for misdiagnosis and consider limitations of available investigations. We propose that diagnostic uncertainty in epilepsy should be more widely acknowledged and addressed, and that this may reduce misdiagnosis rates.

Factors limiting the application of electrical impedance tomography for identification of regional conductivity changes using scalp electrodes during epileptic seizures in humans.

Electrical impedance tomography (EIT) has the potential to produce images during epileptic seizures. This might improve the accuracy of the localization of epileptic foci in patients undergoing presurgical assessment for curative neurosurgery. It has already been shown that impedance increases by up to 22% during induced epileptic seizures in animal models, using cortical or implanted electrodes in controlled experiments. The purpose of this study was to determine if reproducible raw impedance changes and EIT images could be collected during epileptic seizures in patients who were undergoing observation with video-electroencephalography (EEG) telemetry as part of evaluation prior to neurosurgery to resect the region of brain causing the epilepsy. A secondary purpose was to develop an objective method for processing and evaluating data, as seizures arose at unpredictable times from a noisy baseline. Four-terminal impedance measurements from 258 combinations were collected continuously using 32 EEG scalp electrodes in 22 seizure episodes from 7 patients during their presurgical assessment together with the standard EEG recordings. A reliable method for defining the pre-seizure baseline and recording impedance data and EIT images was developed, in which EIT and EEG could be acquired simultaneously after filtering of EIT artefact from the EEG signal. Fluctuations of several per cent over minutes were observed in the baseline between seizures. During seizures, boundary voltage changes diverged with a standard deviation of 1-54% from the baseline. No reproducible changes with the expected time course of some tens of seconds and magnitude of about 0.1% could be reliably measured. This demonstrates that it is feasible to acquire EIT images in parallel with standard EEG during presurgical assessment but, unfortunately, expected EIT changes on the scalp of about 0.1% are swamped by much larger movement and systematic artefact. Nevertheless, EIT has the unique potential to provide invaluable neuroimaging data for this purpose and may still become possible with improvements in electrode design and instrumentation.

Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging?

OBJECTIVE: To determine whether it is worth pursuing surgery for the treatment of epilepsy in patients with normal neuroimaging. METHODS: Two patient populations were studied: (1) 136 consecutive patients who were surgically treated; (2) 105 consecutive patients assessed with chronically implanted intracranial electrodes within the same period. Sixty patients belonged to both groups, and included all 21 patients who had normal neuroimaging. RESULTS: There were no differences in the proportion of patients with favourable outcome between those with normal and those with abnormal neuroimaging, irrespective of whether intracranial recordings were required. Among the 19 operated patients with normal neuroimaging, 74% had a favourable outcome (Engel's seizure outcome grades I and II), and among the 93 patients with abnormal neuroimaging, 73% had favourable outcome (p = 0.96). In patients with temporal resections, 92% of the 13 patients with normal neuroimaging had a favourable outcome, whereas among the 70 patients with abnormal neuroimaging, 80% had a favourable outcome (p = 0.44). In patients with extratemporal resections, two of the six patients with normal neuroimaging had a favourable outcome, while 12 of the 23 patients with abnormal neuroimaging had a favourable outcome (p = 0.65). Among the 105 patients studied with intracranial electrodes, five suffered transitory deficits as a result of implantation, and two suffered permanent deficits (one hemiplegia caused by haematoma and one mild dysphasia resulting from haemorrhage). CONCLUSIONS: It is worth pursuing surgery in patients with normal neuroimaging because it results in good seizure control and the incidence of permanent deficits associated with intracranial studies is low.

Neuropsychiatric porphyria in patients with refractory epilepsy: report of three cases.

OBJECTIVES: Although epileptic seizures are an infrequent feature of acute attacks of the neuropsychiatric porphyrias, there are no significant reports of porphyria in chronic epilepsy. This paper attempts to redress the balance. METHODS: Three case reports, including detailed laboratory and molecular diagnostics. RESULTS: Two patients with variegate porphyria and one with acute intermittent porphyria, referred within 1 year to a specialist porphyria service, with a long history of chronic refractory epileptic seizures, are described. CONCLUSIONS: Porphyria may be an aetiological factor in some cases of chronic refractory partial or generalised epilepsy. Porphyria should also be considered if addition of a new anti-epileptic medication causes a major deterioration in the epilepsy.

VNS in patients with previous unsuccessful resective epilepsy surgery: antiepileptic and psychotropic effects.

OBJECTIVES: To assess the efficacy of vagus nerve stimulation (VNS) in patients with medically and surgically intractable complex partial seizures (CPS). PATIENTS AND METHODS: Sixteen patients with previous temporal [15] and frontal [one] resections were treated with VNS between 1994 and 1999 at King's College Hospital, London, UK. Post-operative video-electroencephalogram telemetry had shown that CPS started from the operated side in 12 patients, contralaterally in three and bilaterally independently in one. RESULTS: Three patients (18.75%) had 50% or more reduction in seizure frequency, but one showed severe worsening of epilepsy, which remitted upon VNS discontinuation. The antiepileptic effect of VNS was not different with respect to the type of operation (anterior temporal lobectomy vs amygdalohippocampectomy), the side of operation, or the side of seizure onset. We observed psychotropic effects in two patients with post-ictal psychosis, in two others with depression, and in a child with severe behavioral disorder. CONCLUSIONS: VNS may have a rather limited antiepileptic role to play in patients with persistent seizures following epilepsy surgery, but may independently possess useful antipsychotic and mood-stabilizing properties.

Postictal psychosis after temporal lobectomy.

Three of 282 consecutive patients who had temporal resections for intractable epilepsy developed postoperative postictal psychosis. These three patients had seizure recurrence contralateral to the resection, whereas none of the patients with ipsilateral seizure recurrence developed any psychiatric symptoms after surgery. Two had left amygdalo-hippocampectomy and one right temporal lobectomy. The de novo occurrence of postoperative postictal psychosis is a well-defined complication of surgery for temporal lobe epilepsy, and may relate to contralateral epileptogenesis.

Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis.

OBJECTIVES: To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. METHODS: The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. RESULTS: At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. CONCLUSIONS: The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.

Predictors of outcome and pathological considerations in the surgical treatment of intractable epilepsy associated with temporal lobe lesions.

OBJECTIVES: To evaluate the influence of clinical, investigative, and pathological factors on seizure remission after temporal lobectomy for medically intractable epilepsy associated with focal lesions other than hippocampal sclerosis. METHODS: From a series of 234 consecutive "en bloc" temporal resections for medically intractable epilepsy performed between 1976 and 1995, neuropathological examination disclosed a focal lesion in 80. The preoperative clinical, neuropsychological, interictal EEG, and neuroimaging characteristics of these patients were assembled in a computerised database. The original neuropathological material was re-examined for lesion classification and completeness of removal. The presence of additional cortical dysplasia and mesial temporal sclerosis was also noted. Survival analysis was performed using Kaplan-Meier curves and actuarial statistics. Logistic regression analysis was used to establish the independent significance of the clinical variables. RESULTS: The probability of achieving a 1 year seizure remission was 71% by 5 years of follow up. Factors predicting a poor outcome on multivariate analysis included the need for special schooling and a long duration of epilepsy. Generalised tonic-clonic seizures, interictal EEG discharges confined to the resected lobe, demonstration of the lesion preoperatively on CT, and complete histological resection of the lesion were not predictive of outcome. Neuropsychological tests correctly predicted outcome in left sided cases but apparently congruent findings in right sided resections were associated with a poor outcome. Pathological reclassification established the dysembryoplastic neuroepithelial tumour as the commonest neoplasm (87%) in this series, with a significantly better seizure outcome than for developmental lesions, such as focal cortical dysplasia. CONCLUSIONS: The findings highlight the importance of dysembryoplastic neuroepithelial tumour in the pathogenesis of medically refractory lesional temporal lobe epilepsy and the prognostic significance of preoperative duration of epilepsy emphasises the need for early recognition and surgical treatment. Cognitive and behavioural dysfunction, however, is associated with a lower seizure remission rate, independent of duration of epilepsy.

Chronic encephalitis and temporal lobe epilepsy: a variant of Rasmussen's syndrome?

The authors report two adult patients with chronic temporal lobe epilepsy and pathologic features consistent with Rasmussen's encephalitis. Although seizures persisted after temporal lobe surgery no progressive cognitive or neurologic deficit has emerged. Prominent auditory auras in each suggested a persisting epileptogenic focus in the superior temporal gyrus. The current findings expand the clinical spectrum of Rasmussen's encephalitis and suggest that chronic nonprogressive encephalitis may serve as the pathologic substrate of medically intractable temporal lobe epilepsy.

Lateralizing and localizing values of ictal onset recorded on the scalp: evidence from simultaneous recordings with intracranial foramen ovale electrodes.

PURPOSE: The value of scalp recordings to localize and lateralize seizure onset in temporal lobe epilepsy has been assessed by comparing simultaneous scalp and intracranial foramen ovale (FO) recordings during presurgical assessment. The sensitivity of scalp recordings for detecting mesial temporal ictal onset has been compared with a "gold standard" provided by simultaneous deep intracranial FO recordings from the mesial aspect of the temporal lobe. As FO electrodes are introduced via anatomic holes, they provide a unique opportunity to record simultaneously from scalp and mesial temporal structures without disrupting the conducting properties of the brain coverings by burr holes and wounds, which can otherwise make simultaneous scalp and intracranial recordings unrepresentative of the habitual EEG. METHODS: Simultaneous FO and scalp recordings from 314 seizures have been studied in 110 patients under telemetric presurgical assessment for temporal lobe epilepsy. Seizure onset was identified on scalp records while blind to recordings from FO electrodes and vice versa. RESULTS: Bilateral onset (symmetric or asymmetric) was more commonly found in scalp than in FO recordings. The contrary was true for unilateral seizure onset. In seizures with bilateral asymmetric onset on the scalp, the topography of largest-amplitude scalp changes at onset does not have localizing or lateralizing value. However, 75-76% of seizures showing unilateral scalp onset with largest amplitude at T1/T2 or T3/T4 had mesial temporal onset. This proportion dropped to 42% among all seizures with a unilateral scalp onset at other locations. Of those seizures with unilateral onset on the scalp at T1/T2, 65.2% showed an ipsilateral mesial temporal onset, and 10.9% had scalp onset incorrectly lateralized with respect to the mesial temporal onset seen on FO recordings. In seizures with a unilateral onset on the scalp at electrodes other than T1/T2, the proportions of seizures with correctly and incorrectly lateralized mesial temporal onset were 37.5 and 4.2%, respectively. Thus the ratio between incorrectly and correctly lateralized mesial temporal onsets is largely similar for seizures with unilateral scalp onset at T1/T2 (16.7%) and for seizures with unilateral scalp onset at electrodes other than T1/T2 (11.2%). The onset of scalp changes before the onset of clinical manifestations is not associated with a lower proportion of seizures with bilateral onset on the scalp, or with a higher percentage of mesial temporal seizures or of mesial temporal seizures starting ipsilateral to the side of scalp onset. In contrast, the majority (78.4%) of mesial temporal seizures showed clinical manifestations starting after ictal onset on FO recordings. CONCLUSIONS: A bilateral scalp onset (symmetric or asymmetric) is compatible with a mesial temporal onset, and should not deter further surgical assessment. Although a unilateral scalp onset at T1/T2 or T3/T4 is associated with a higher probability of mesial temporal onset, a unilateral onset at other scalp electrodes does not exclude mesial temporal onset. A unilateral scalp onset at electrodes other than T1/T2 is less likely to be associated with mesial temporal onset, but its lateralizing value is similar to that of unilateral scalp onset at T1/T2. The presence of clinical manifestations preceding scalp onset does not reduce the localizing or lateralizing values of scalp recordings.

Failed surgery for epilepsy. A study of persistence and recurrence of seizures following temporal resection.

From a series of 282 consecutive temporal resections for medically intractable epilepsy associated with mesial temporal sclerosis (MTS), dysembryoplastic neuroepithelial tumour (DNT) or non-specific pathology (NSP), 51 patients had persistent or recurrent seizures occurring at least monthly. Of these patients, 44 underwent detailed assessment of their postoperative seizures, which included clinical evaluation, interictal and ictal EEG and high-resolution MRI. Of the 20 patients with MTS in the original pathology, 14 (70%) had postoperative seizures arising in the hemisphere of the resection, the majority (12 patients) in the temporal region. Although MRI demonstrated residual hippocampus in five of these 12 patients, only one patient was considered to have seizures arising there, whilst the remainder had electroclinical evidence of seizure onset in the neocortex. In contrast, five of the MTS relapses (25%) had seizure onset exclusively in the contralateral temporal region. Among the 14 patients with non-specific pathology, relapse was also predominantly from the ipsilateral hemisphere (64%), but more relapsed from extratemporal sites compared with the MTS cases, including two with NSP who had occipital structural abnormalities. Although 70% of the 10 patients with DNT had postoperative partial seizures arising in the ipsilateral hemisphere, many (60%) had evidence of a more diffuse disorder with additional generalized seizures, cognitive and behavioural disturbance and multifocal and generalized EEG abnormalities. Nine patients (20%) had immediate postoperative seizure-free periods of at least 1 year, and seven of these had MTS in the operative specimen. Of these seven patients, four had ipsilateral temporal seizures and three had contralateral temporal seizures. Overall, few missed lesions were discovered on postoperative MRI and reoperations were performed or considered possible in a minority of cases. Despite well-defined preoperative electroclinical syndromes of temporal lobe epilepsy, many patients relapsed unexpectedly, either immediately or remotely from the time of surgery. Maturing epileptogenicity in a surgical scar was not, however, considered to be a significant primary mechanism in patients who relapsed after a seizure-free interval.

Sources of error in comparing functional magnetic resonance imaging and invasive electrophysiological recordings.

OBJECT: Several authors have recently reported studies in which they aim to validate functional magnetic resonance (fMR) imaging against the accepted gold standard of invasive electrophysiological monitoring. The authors have conducted a similar study, and in this paper they identify and quantify two characteristics of these data that can make such a comparison problematic. METHODS: Eight patients in whom surgery for epilepsy was performed and five healthy volunteers underwent fMR imaging to localize the part of the sensorimotor cortex responsible for hand movement. In the patient group subdural electrode mats were subsequently implanted to identify eloquent regions of the brain and the epileptogenic zone. The fMR imaging data were processed to correct for motion during the study and then registered with a postimplantation computerized tomography (CT) scan on which the electrodes were visible. The motion during imaging in the two groups studied, and the deformation of the brain between the preoperative images and postoperative scans were measured. The patients who underwent epilepsy surgery moved significantly more during fMR imaging experiments than healthy volunteers performing the same motor task. This motion had a particularly increased out-of-plane component and was significantly more correlated with the stimulus than in the volunteers. This motion was especially increased when the patients were performing a task on the side affected by the lesion. The additional motion is hard to correct and substantially degrades the quality of the resulting fMR images, making it a much less reliable technique for use in these patients than in others. Also, the authors found that after electrode implantation, the brain surface can shift more than 10 mm relative to the skull compared with its preoperative location, substantially degrading the accuracy of the comparison of electrophysiological measurements made in the deformed brain and fMR studies obtained preoperatively. CONCLUSIONS: These two findings indicate that studies of this sort are currently of limited use for validating fMR imaging and should be interpreted with care. Additional image analysis research is necessary to solve the problems caused by patients' motion and brain deformation.

Thalamic changes with mesial temporal sclerosis: MRI.

We reviewed the preoperative images of 28 patients with pathologically proven mesial temporal sclerosis, to assess thalamic asymmetry and signal change. A further 25 nonsurgical patients with temporal lobe epilepsy and unequivocal, unilateral changes of mesial temporal sclerosis, and 20 controls, were also reviewed. None of the control group had unequivocal asymmetry of the thalamus. There was an ipsilateral asymmetrically small thalamus in five (18%) of the surgical group and in three (12%) of the nonsurgical patients. In four cases there was thalamic signal change. In three patients with thalamic volume loss there was ipsilateral hemiatrophy. All patients with an asymmetrically small thalamus had an asymmetrically small fornix and all but one a small ipsilateral mamillary body.

Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy.

OBJECTIVE: To assess the clinical implications and the pathophysiologic determinants of interictal bitemporal hypometabolism (BTH) in temporal lobe epilepsy (TLE) not associated with bilateral MRI abnormalities or intracranial space-occupying lesions. METHODS: The authors compared the clinical, interictal, and ictal EEG, Wada test, and neuropsychology data of 15 patients with intractable complex partial seizures of temporal lobe origin and BTH with those of 13 consecutive patients with unilateral TLE associated with unilateral temporal hypometabolism (UTH) who remained seizure free for more than 3 years after anterior temporal lobectomy. 18F-fluorodeoxyglucose PET scans were analyzed visually and semiquantitatively, and ratios of counts in individual temporal areas to the rest of the cerebrum were compared with the corresponding values from 11 normal control subjects and with the nonepileptogenic hemisphere of the 13 patients with UTH. BTH was defined as more than 2.5 SDs below control values for two or more temporal areas on each side irrespective of any asymmetry. RESULTS: BTH reflected bilateral independent seizure onset in eight patients (53%). The topography of the metabolic depression was not a reliable predictor of epileptogenicity, but involvement of the inferior temporal gyrus was related specifically to ipsilateral seizure onset (70% sensitivity, 100% specificity). In patients with unilateral TLE, contralateral hypometabolism was associated with longer disease duration and worst memory performance during the Wada test, which amounted to global amnesia after ipsilateral injection in three patients, precluding surgical treatment. Contralateral seizure spread in the ictal EEG was significantly faster in patients with BTH. CONCLUSIONS: In TLE, symmetric or asymmetric BTH may signal bilateral independent seizure onset in approximately half the patients, especially when involving the inferior temporal gyrus. Alternatively, it may reflect an advanced stage of the disease process, characterized by a breakdown of the inhibitory mechanisms in the contralateral hemisphere, and secondary memory deficit associated with higher risk of postoperative memory decline. Patients with TLE and BTH but without bilateral MRI changes may still be operated on successfully, but surgical suitability should be proved by comprehensive intracranial EEG studies and Wada test.

N-Acetylaspartate and creatine levels measured by (1)H MRS relate to recognition memory.

OBJECTIVES: To investigate the relationship between recognition memory and metabolite levels in medial structures of the temporal lobes in the living human brain. METHODS: Proton MRS ((1)H MRS) and the intracarotid amobarbital test were performed in 16 epileptic patients found suitable for temporal lobectomy. All patients had mesial temporal sclerosis. Metabolite ratios between N:-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline-containing compounds (Cho) [NAA/(Cr + PCr), NAA/Cho, and NAA/(Cr + PCr + Cho)] were calculated for (1)H MRS voxels that included the amygdala, anterior half of the hippocampus, and underlying subiculum. Metabolite ratios were correlated with unilateral memory scores estimated by the intracarotid amobarbital test for words, objects, faces, and total score. RESULTS: The total memory score, memory for objects and faces, and NAA/(Cr + PCr) were significantly lower for the hemisphere ipsilateral to the resection. The asymmetry indexes for NAA/(Cr + PCr) correlated with asymmetry indexes for words (rho = 0.82, p = 0.0001) and total memory (rho = 0. 72, p = 0.002). Analysis of memory scores and metabolite ratios from all 32 hemispheres revealed a correlation between NAA/(Cr + PCr) and memory for words (rho = 0.45, p = 0.009). A correlation between memory for words and NAA/(Cr + PCr) existed in the contralateral (rho = 0.58, p = 0.019) and in the right (rho = 0.51, p = 0.045) hemispheres, and a trend was found in the left hemispheres (rho = 0. 48, p = 0.06). CONCLUSION: There is a correlation between memory for words and the NAA/(Cr + PCr) ratio from medial temporal structures in patients with mesial temporal sclerosis. The findings suggest that medial temporal structures and adjacent neocortex play a significant role in recognition memory in humans, particularly for words.