Regional changes in hippocampal T2 relaxation and volume: a quantitative magnetic resonance imaging study of hippocampal sclerosis

OBJECTIVE: The principal MRI features of hippocampal sclerosis are volume loss and increased T2 weighted signal intensity. Minor and localised abnormalities may be overlooked without careful quantitation. Hippocampal T2 relaxation time (HT2) can be quantified, but previously has only been measured on a few thick coronal slices with interslice gaps. In this study HT2 was measured along the entire length of the hippocampus on contiguous slices and used, with quantitative measures of hippocampal volume (HV) and distribution of atrophy, to better define the range of hippocampal sclerosis. METHODS: Thirty patients with temporal lobe epilepsy, 10 patients with extratemporal localisation related epilepsy and extratemporal lesions, and 20 control subjects were studied using MRI T2 relaxometry and volumetry. RESULTS: In controls and patients, HT2 was higher in the anterior than the posterior hippocampus. Using HV, morphometric, and HT2 data, patients with temporal lobe epilepsy were classified as unilateral diffuse hippocampal sclerosis (n=16), unilateral focal (n=6), bilaterally affected (n=6), and normal (n=2). In patients with unilateral hippocampal sclerosis, the anterior hippocampus was always affected. In three patients with normal HV, HT2 measurements disclosed unilateral focal abnormalities that corresponded to the EEG lateralisation of epileptic activity. Patients with bilateral hippocampal involvement had an earlier onset of epilepsy than patients with unilateral hippocampal sclerosis. CONCLUSIONS: Measurement of regional abnormalities of HT2 along the length of the hippocampus provides further refinement to the MRI assessment of the hippocampi in patients with temporal lobe epilepsy and is complementary to volumetric and morphological data.     

Hemicranial volume deficits in patients with temporal lobe epilepsy with and without hippocampal sclerosis

PURPOSE: In patients with refractory temporal lobe epilepsy, studies have suggested volume deficits measured by MRI of brain structures outside the epileptogenic hippocampus. Hippocampal sclerosis (HS) is a frequent, but not obligate, finding in such patients. The present study examines the influence of the presence of HS on quantitative magnetic resonance imaging (MRI) measurements. METHODS: We analyzed 47 patients and 30 controls by quantitative MRI, including intracranial volume (ICV), hemicranial volume, hippocampal volume (HCV), and T2 relaxometry. MRI results were compared with histological findings in the resected temporal lobe. RESULTS: Histology documented HS in 35 patients (HS group) and other findings in 12 patients (no-HS group). In both groups, the hemicranial volume ipsilateral to the epileptogenic focus was significantly smaller than on the contralateral side (p < 0.004). The HCV on both sides was smaller in the HS group compared with patients without HS (p < or = 0.004). Unilateral hippocampal atrophy and increased T2 value were found in 71% of patients with HS, and bilaterally normal HCV and T2 value were found in 67% of patients without HS. CONCLUSIONS: The smaller hemicranial volume on the focus side, irrespective of the presence or absence of HS suggests a different pathogenic mechanism for the additional hemicranial volume deficit, compared to HS itself. The contralateral HCV deficit depends on the presence of HS, indicating a pathogenic connection between damage to both hippocampi.     

ILAE-defined epilepsy syndromes in children: correlation with quantitative MRI

PURPOSE: The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippocampal asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (MTLE) from other partial and generalized epileptic syndromes in children. METHODS: Seventy children were enrolled; entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE. RESULTS: Control data revealed symmetric hippocampi, mean smaller/larger ratio of 0.96 (0.95-0.97, 95% CI) with no gender or right/left predominance. Overall 23% of patients had significant HA. Mean hippocampal ratio for MTLE was 0.78 (95% CI, 0.70-0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors. CONCLUSIONS: In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.     

Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study

OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.     

Dynorphin and the kappa 1 ligand [3H]U69,593 binding in the human epileptogenic hippocampus

The distribution of dynorphin (DYN), one of its binding sites (kappa 1 receptor) and their relationship to neuronal loss and granule cell hyperexcitability was examined in hippocampi from patients with temporal lobe epilepsy (TLE). In hippocampi that were not the seizure focus (mass associated temporal lobe epilepsy, MaTLE; and paradoxical temporal lobe epilepsy, PTLE) DYN-like immunoreactivity was localized in the dentate granule cells and their mossy fiber terminals within the hilus and area CA3. In hippocampi that were the seizure focus (MTLE), 89% showed an additional band of immunoreactivity confined to the inner molecular layer (IML) of the dentate gyrus, representing recurrent mossy fiber collaterals. In 11% of MTLE patients no staining was found in the IML (MTLE/DYN-). The MTLE/DYN- hippocampi were also characterized by a significantly lower degree of cell loss than in MTLE hippocampi in the dentate granule cell layer, the hilus and CA3. Both MTLE and MTLE/DYN- hippocampi showed evoked epileptiform bursting in granule cells while MTLE showed greater polysynaptic EPSPs and spontaneous excitatory activity. Thus granule cell recurrent collateral sprouting may account for only some aspects of hyperexcitability. In 30% of the MTLE group, hilar neurons of a variety of morphological types expressed DYN immunoreactivity in their somata and dendrites. The density of [3H]U69,593 binding sites in MaTLE and PTLE patients was highest in areas CA1 and the subiculum-regions having little or no DYN-staining. In the dentate molecular layer, hilus and CA3--regions with the most DYN immunoreactivity--there was a low density of ligand binding. The significance of this transmitter/receptor mismatch is yet unknown.     

Clinical correlations with hippocampal atrophy

There is now a consensus that magnetic resonance imaging (MRI) is a sensitive and specific indicator of mesial temporal sclerosis (MTS) in patients with partial epilepsy. MTS is the most common pathological finding underlying the epileptogenic zone in patients undergoing temporal lobe surgery for medically refractory partial seizures. MRI-based hippocampal volumetric studies (i.e., quantitative MRI), has been shown to provide objective evidence for hippocampal atrophy in patients with MTS. The hippocampal volume in the epileptic temporal lobe has correlated with the neuronal cell densities in selected hippocampal subfields. A history of febrile seizures in childhood and age of unprovoked seizure onset have been associated with MRI-based hippocampal volumetry. There is conflicting evidence regarding the relationship between the duration of the seizure disorder and volumetry. Quantitative MRI has compared favorably to other noninvasive techniques (e.g., scalp-recorded EEG), in indicating the diagnosis of medical temporal lobe epilepsy (MTLE). MRI-identified hippocampal atrophy has also been a favorable prognostic indicator of seizure outcome after temporal lobe surgery. The presence of hippocampal atrophy appears to serve an in vivo surrogate for the presence of MTS.     

Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy

To determine whether lesional neocortical temporal lobe epilepsy (NTLE) can be differentiated from mesial temporal lobe epilepsy (MTLE) during the noninvasive presurgical evaluation, we compared the historical features, seizure symptomatology, and surface EEG of 8 patients seizure free after neocortical temporal resection with preservation of mesial structures and 20 patients after anterior temporal lobectomy for MTLE. Seizure symptomatology of 107 seizures (28 NTLE, 79 MTLE) was analyzed. One hundred one ictal EEGs (19 NTLE, 82 MTLE) were reviewed for activity at seizure onset; presence, distribution, and frequency of lateralized rhythmic activity (LRA); and distribution of postictal slowing. Seizure symptomatology and EEG data were compared between groups, and sensitivity, specificity, and positive and negative predictive values were determined for variables that differed significantly. Multiple logistic regression was used to determine whether patients could be correctly classified as having MTLE or NTLE. MTLE patients were younger at onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications, or head injury. NTLE seizures lacked features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation, and postictal cough or sigh. NTLE ictal EEG recordings demonstrated lower mean frequency of LRA that frequently had a hemispheric distribution, whereas LRA in MTLE seizures was maximal over the ipsilateral temporal region. We conclude that it may be possible to differentiate lesional NTLE from MTLE on the basis of historical features, seizure symptomatology, and ictal surface EEG recordings. This may assist in the identification of patients with medically refractory nonlesional NTLE who frequently require intracranial monitoring and more extensive or tailored resections.     

The effects of New York''s bypass surgery provider profiling on access to care and patient outcomes in the elderly

OBJECTIVES: To determine the annual rates of volumetric change of the hippocampus and temporal horn in cognitively normal elderly control subjects and individually matched patients with AD, and to test the hypothesis that these rates were different. BACKGROUND: Cross-sectional studies consistently reveal cerebral atrophy in elderly nondemented subjects compared with healthy young adults, and greater atrophy in patients with AD relative to elderly control subjects. However, rates of atrophy are estimated most accurately by performing serial measurements in the same individuals. METHODS: MRI-based volumetric measurements of the hippocampi and temporal horns were performed in 24 cognitively normal subjects aged 70 to 89 years who were individually matched with respect to gender and age with 24 patients with AD. Each subject underwent an MRI protocol twice, separated by 12 months or more. RESULTS: The mean annual rate of hippocampal volume loss among control subjects was -1.55+/-1.38% and the temporal horns increased in volume by 6.15+/-7.69% per year. These rates were significantly greater among AD patients: hippocampus, -3.98+/-1.92% per year, p < 0.001; temporal horn, 14.16+/-8.47% per year, p = 0.002. CONCLUSION: A statistically significant yearly decline in hippocampal volume and an increase in temporal horn volume was identified in elderly control subjects who represent typical aging individuals. These rates were approximately 2.5 times greater in patients with AD than in individually age- and gender-matched control subjects.     

FDG-PET and volumetric MRI in the evaluation of patients with partial epilepsy

We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.     

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy (1H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups had smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.

The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis

By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect.     

Corpora amylacea in hippocampal sclerosis

Corpora amylacea have been reported in around 60% of hippocampal sclerosis specimens. The aim was to determine whether there are clinical and quantitative hippocampal MRI differences between hippocampal sclerosis with and without corpora amylacea. Corpora amylacea density was determined in 46 resected hippocampi of patients with temporal lobe epilepsy, using a three dimensional microscopical counting technique. Forty one hippocampi had hippocampal sclerosis. Twenty six of the 41 (63%) hippocampal sclerosis specimens contained corpora amylacea, which were found in highest numbers in the CA1 subregion of the hippocampus. Corpora amylacea density in the CA1 correlated inversely with the neuronal density in CA1. Hippocampal sclerosis with corpora amylacea had the same clinical and quantitative hippocampal MRI characteristics as hippocampal sclerosis without corpora amylacea, and did not affect seizure outcome after surgery adversely. In conclusion, formation of corpora amylacea seems to be a pathological response to neuronal cell loss in most hippocampal sclerosis specimens, with no clear clinical and quantitative hippocampal MRI correlates.     

Severe amnesia: an usual late complication after temporal lobectomy

A patient developed the severe amnesic syndrome 8 years after temporal lobe surgery for epilepsy. He underwent left temporal lobectomy (6 cm, 43.5 g; hippocampal sclerosis) aged 19, and remained seizure free for 8 years until a convulsion followed a head injury. He became severely amnesic after a fourth convulsion 16 months later. He was right-handed, pre-operative IQ was average, verbal memory poor and non-verbal memory normal. Post-operatively, these were unchanged. After the first post-operative seizure he began professional training. After onset of amnesia IQ was unchanged, anterograde memory severely impaired and retrograde amnesia dense for at least 16 months. He died 2 years later. Magnetic resonance imaging before amnesia showed absence of anterior left temporal lobe, atrophy of left fornix and mamillary body, and normal right temporal lobe. Four months after onset of amnesia, right hippocampal volume had reduced by 36%. Autopsy showed: previous left temporal lobectomy with absence of left amygdala and hippocampus, atrophy of fornix and mamillary body; neuronal loss in the right hippocampus, severe in CA1 and CA4; intact right amygdala and parahippocampal gyrus; recent diffuse damage associated with cause of death. A convulsion can cause severe hippocampal damage in adult life. Hippocampal zones CA1 and/or CA4 are critical for maintaining memory and the amygdala and parahippocampal gyrus cortex alone cannot support acquisition of new memories.     

Nutrition in infancy: implications for practice

The aim of the present study was to assess selective atrophy of the temporal lobe and amygdala in the early stages of Alzheimer dementia (AD). Magnetic resonance imaging (MRI) measurements and the presence of highsignal lesions (HSL) were analysed in 31 patients with mild to moderate probable AD and 22 controls. In the AD group, MRI findings were compared with cognitive variables and specific features of memory functions. Alzheimer patients showed a significant reduction in volumetric measurement compared with controls in the total volume (P < 0.01), temporal lobe (P < 0.01) and amygdala (P < 0.05). The temporal lobe/brain volume ratio was also significantly reduced in AD subjects (P < 0.05). Atrophy of temporal structures was significantly related to the degree of episodic and semantic memory impairment according to a material-specific effect. No significant correlations between amygdala and cognitive variables were found. The results of our study confirm the usefulness of measures of temporal lobe atrophy assessed with MRI in the diagnosis of AD. In contrast, HSL are relatively common in AD patients (12/31 cases) and were not related to volumetric findings, severity of dementia or functional disability.     

Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.     

Selective spatial memory impairment after right unilateral temporal lobectomy

Deficits in performance of both spatial and visual tasks are common following tissue loss in the right temporal lobe. Since spatial and visual attributes are frequently confounded in experimental tasks, we have studied patients following unilateral temporal lobectomy, in an attempt to determine which aspect mediates the observed deficits. Spatial and visual memory performance was compared in normal controls (n = 16), left temporal (LTL; n = 19) and right temporal (RTL; n = 19) lobectomy patients, by presentation of eight abstract designs in a spatial array for subsequent recall and recognition of the designs (visual memory) and recall of their spatial position (spatial memory). By varying the retention intervals for each group, all three groups were matched on both recall and recognition of the designs at sub-ceiling levels. In contrast, recall of the position of the designs (spatial memory), tested at equivalent delays to those of the visual memory tests, revealed a deficit in the RTL patients compared to both controls and LTL patients (p < 0.05). Magnetic resonance imaging (MRI) was used to quantify the extent of resection of the hippocampus and parahippocampal regions in the two patient groups and showed a significant correlation between hippocampal and parahippocampal removal and spatial memory in the RTL group only. These data support the notion of a disproportionately large involvement of the right hippocampus and adjacent regions in spatial memory.     

Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic images

Magnetic resonance spectroscopic imaging (MRSI) is capable of determining the spatial distribution in vivo of cerebral metabolites, including N-acetylaspartate (NAA), a compound found only in neurons. We used this technique in 10 patients with temporal lobe epilepsy (TLE) to determine the location of maximal neuronal/axonal loss or damage and to evaluate the potential of MRSI for presurgical lateralization. Asymmetry of the relative resonance intensity of NAA to creatine was determined for mid and posterior regions of the temporal lobes defined anatomically and also for "metabolic lesions" defined as the regions of maximal abnormality on MRSI. MRSI revealed decreased relative signal intensity in at least one temporal lobe of all patients. Two patients had a widespread reduction in NAA in both temporal lobes. The region of maximal abnormality was usually in the posterior temporal lobe but sometimes in the mid temporal lobe. The side of lowest NAA was ipsilateral to the clinical electroencephalographic lateralization in all patients. Lateralization based on NAA to creatine correlated with the atrophy of amygdala and hippocampus in 8 patients who showed this on magnetic resonance imaging volumetric measurements. MRSI can demonstrate regional neuronal loss or damage that correlates with clinical electroencephalographic and structural lateralization in temporal lobe epilepsy. The ability to identify a region of maximal metabolic abnormality on spectroscopic images may confer greater sensitivity than that available from single voxel methods. The maximal metabolic abnormality may not be located in a voxel defined a priori, and based on anatomical considerations, without knowledge of the distribution of the metabolic abnormality.