Small temporal pole encephaloceles: A treatable cause of “lesion negative” temporal lobe epilepsy

Epilepsy due to encephaloceles of the temporal pole may be an under recognized, treatable cause of refractory temporal lobe epilepsy (TLE). We describe three adult patients initially labeled “lesion negative” TLE. In all, video–electroencephalography (EEG) revealed ictal theta in the left temporal region and positron emission tomography (PET) showed temporal lobe hypometabolism, but neuropsychology revealed preserved verbal memory. Close inspection of structural magnetic resonance imaging (MRI) suggested subtle abnormalities at the tip of the left temporal lobe. High resolution computed tomography (CT) confirmed bony defects in the inner table of the skull. 3T MRI with fine coronal and sagittal slices indicated cerebrospinal fluid (CSF) and brain tissue protruding into the defects. All proceeded to resection of the temporal tip and became seizure free. Patients with “lesion negative” TLE should have careful review of images covering the temporal pole. If encephalocele is suspected, further imaging with high‐resolution CT and MRI can be helpful. Temporal polar resection, sparing mesial structures, appears to be curative.     

Entorhinal cortex MRI assessment in temporal,extratemporal, and idiopathic generalized epilepsy

PURPOSE: We previously showed a reduction in the volume of the entorhinal cortex (EC) ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy (TLE). The purpose of this study was to examine the specificity of EC atrophy in epilepsy. METHODS: We performed volumetric measurement of the EC on high-resolution magnetic resonance imaging (MRI) in patients with TLE (n = 70), extratemporal lobe epilepsy (ETE; n = 18), and idiopathic generalized epilepsy (IGE; n = 20). EC volumes of epilepsy patients were compared with those of 48 age- and sex-matched normal controls. Within the TLE group, 63 patients were selected prospectively with hippocampal atrophy ipsilateral to the seizure focus. The remaining seven patients were chosen retrospectively based on normal volumetric MRI of the hippocampus and amygdale, as well as normal histopathologic examination of the resected tissue. RESULTS: Compared with normal controls, EC volume was smaller ipsilateral but not contralateral to the seizure focus in patients with TLE (p < 0.001). No difference in the EC volumes ipsilateral and contralateral to the seizure focus was seen in patients with ETE and IGE compared with normal controls. The individual analysis showed that the EC was atrophic in 73% of TLE patients with hippocampal atrophy. Three of the seven TLE patients with normal volumetric MRI of the hippocampus and amygdala and normal histopathologic examination had EC atrophy ipsilateral to the seizure focus. In no patient with ETE or IGE was the EC found to be atrophic. CONCLUSIONS: EC atrophy ipsilateral to the seizure focus appears to be specific to mesial temporal lobe structural damage associated with TLE.     

MRI对颞叶癫痫的定侧诊断的价值

目的 观察颞叶癫痫患者的头颅MRI变化，探讨MRI对颞叶癫痫的定侧诊断价值。方法 采用头颅MRI检查，对40例颞叶癫痢患者及40例正常对照组的海马体积进行测量，将海马萎缩严重侧作为致瘌侧。结果 定量MRI对颞叶癫痢定侧敏感性为72．5％，特异性为85．3％。结论 头颅MRI扫描对颞叶癫痫的定位及定侧有着重要的诊断价值。     

Early MR diffusion and relaxation changes in the parahippocampal gyrus precede the onset of spontaneous seizures in an animal model of chronic limbic epilepsy

Structural changes in limbic regions are often observed in individuals with temporal lobe epilepsy (TLE) and in animal models. However, the brain structural changes during the evolution into epilepsy remain largely unknown. Therefore, the purpose of this study was to define the temporal changes in limbic structures after experimental status epilepticus (SE) during the latency period of epileptogenesis in vivo, with quantitative diffusion tensor imaging (DTI) and T2 relaxometry in an animal model of chronic TLE. A pair of fifty micron electrodes was implanted into the ventral hippocampus in twelve male adult rats. Self-sustaining SE was induced with electrical stimulation in eleven rats. Three rats served as age-matched controls. In vivo diffusion tensor and T2 magnetic resonance imaging (MRI) was performed at 11.1 Tesla, pre- and post-implantation of electrodes and 3, 5, 7, 10, 20, 40 and 60 days post-SE to assess structural changes. Spontaneous seizures were identified with continuous time-locked video-monitoring. Following imaging in vivo, fixed, excised brains were MR imaged at 17.6 Tesla. Subsequently, histological analysis was correlated with MRI results. Following SE, 8/11 injured rats developed spontaneous seizures. Unique to these 8 rats, early T2, diffusivity and anisotropy changes were observed in vivo within the parahippocampal gyrus (contralateral) and fimbria (bilateral). In excised brains, bilateral increase in anisotropy was observed in the dentate gyrus, corresponding to mossy fiber sprouting as determined by Timm staining. Using T2 relaxometry and DTI, specific transient and long-term structural changes were observed only in rats that developed spontaneous limbic seizures.     

Performance in recognition memory is correlated with entorhinal/perirhinal interictal metabolism in temporal lobe epilepsy

In addition to the hippocampus, the entorhinal/perirhinal cortices are often involved in temporal lobe epilepsy (TLE). It has been proposed that these anterior parahippocampal structures play a key role in recognition memory. We studied the voxel-based PET correlation between number of correctly recognized targets in a new recognition memory paradigm and interictal cerebral metabolic rate for glucose, in 15 patients with TLE with hippocampal sclerosis. In comparison to healthy subjects, patients had decreased recognition of targets (P<0.001) and ipsilateral hypometabolism (relative to side of hippocampal sclerosis) of the hippocampus, entorhinal/perirhinal cortices, medial temporal pole, and middle temporal gyrus (P<0.05, corrected by false discovery rate method). Performance correlated with interictal metabolism of ipsilateral entorhinal/perirhinal cortices (P<0.005, Spearman's rank test), but this relationship was not significant in the hippocampus itself (P>0.18, Spearman's rank test). These findings highlight the preferential involvement of entorhinal/perirhinal cortices in recognition memory in patients with TLE, and suggest that recognition memory paradigms may be useful in assessing anterior parahippocampal functional status in TLE.     

Improved Sensitivity of 18FDG-Positron Emission Tomography Scans in Frontal and “Frontal Plus” Epilepsy

Summary We evaluated three techniques of analyzing ¹⁸FDG-positron emission tomography-(PET) scans in 23 cases of presumed frontal lobe epilepsy (FLE): routine visual or “qualitative linear,”“qualitative normalized,” and quantitative normalized approaches. Patients were then classified as having pure frontal, probable frontal, frontoparietal and frontotemporal epilepsy based on prolonged surface EEG monitoring with video, magnetic resonance imaging (MRI), chronic intracranial recording (CIR), and results of surgical excision. Overall sensitivity and accuracy of the scans was 52 and 48% for qualitative linear analysis, which was equivalent to that of MRI, and 69 and 43% for qualitative normalized analysis. Quantitative normalized analysis had 96% sensitivity and 74–78% accuracy and also detected 9 of 11 (81%) abnormalities in nonlesional cases, improving routine sensitivity from 1 of 11 (9%). We conclude that qualitative linear (routine) analysis is inadequate for diagnosis of FLE lobe or “frontal-plus” epilepsies and does not add to the MRI scan. Because qualitative normalized images improve on routine analysis only slightly, quantitative techniques should be applied for preoperative evaluations.     

磁共振成像阴性颞叶癫痫的临床特点分析

目的探讨磁共振成像(MRI)阴性颞叶癫痫(nonlesional temporal lobe epilepsy,TLE-NL)患者的临床特征、记忆水平和影像学特点。方法纳入2012年9月1日至2017年8月31日在浙江大学医学院附属第二医院确诊的44例单侧TLE-NL患者和53例同期就诊单侧颞叶癫痫伴海马硬化(temporal lobe epilepsy with hippocampal sclerosis,TLE-HS)患者,对TLE-NL和TLE-HS的临床特点进行对比。同时纳入20名健康志愿者作为正常对照组。采用韦氏记忆量表评估患者和对照组记忆功能,并通过高分辨率MRI定量分析海马体积及形态,评估TLE-NL和TLE-HS患者记忆水平和海马体积的改变。结果TLE-NL患者比TLE-HS患者发病年龄更晚[(24.3±12.6)岁与(15.8±10.3)岁;t=3.684,P<0.01],癫痫病程更短[4.00(2.00,8.75)年与14.00(7.50,22.00)年;Z=-4.675,P<0.01],热性惊厥史比例[4.5%(2/44)与62.3%(33/53);χ2=32.270,P<0.01)和药物难治性比例更低[47.7%(21/44)与84.9%(45/53);χ2=15.282,P<0.01)。TLE-NL患者在性别比例、癫痫家族史、致痫灶侧别、先兆发生率、症状学类型及发作频率上与TLE-HS患者类似。TLE-NL患者与正常对照组相比无明显记忆损害(记忆商数:105.2±17.4与103.8±16.2;P=1.000),而TLE-HS患者与正常对照组相比存在明显记忆损害(记忆商数:84.5±20.3与103.8±16.2;P<0.01)。TLE-NL患者海马体积和形态与正常对照组相比无明显改变,而TLE-HS患者存在明显致痫灶同侧海马萎缩[(2953±481)mm3与(4431±505)mm3;P<0.01),形态分析结果提示萎缩以海马头及海马体部明显。结论TLE-NL是一类有别于TLE-HS的颞叶癫痫综合征,具有发病年龄晚、病程短、热性惊厥史少、药物难治性癫痫发生率较低、无明显记忆损害及海马萎缩的临床特点。     

EEG background delta activity in temporal lobe epilepsy: correlation with volumetric and spectroscopic imaging

PURPOSE: With quantitative electroencephalogram (EEG) and neuroimaging methods, we examined delta activity, atrophy, and neuronal-axonal dysfunction of the cerebral gray and white matter in patients with intractable temporal lobe epilepsy (TLE). Based on evidence that lesions of the white matter result in EEG delta activity, we postulated that background abnormalities in patients with TLE are related to changes of the temporal lobe white matter. METHODS: We measured interictal delta activity in 34 TLE patients and 10 controls. Spike-free and artifact-free EEG samples were selected by visual inspection. A spectral analysis was used to compute the energy in the delta frequency band. We compared the results of the spectral analysis to magnetic resonance imaging- (MRI) based volumes of the temporal lobe white and gray matter, the hippocampus and the amygdala; and N-acetyl aspartate (NAA) in the lateral and posterior temporal lobe by using proton magnetic resonance spectroscopic imaging (1H-MRSI). The degree of correlation between delta activity and the neuroimaging measurements was assessed by using the Pearson correlation coefficient (r). An analysis of variance (ANOVA) was used to examine the influence of the seizure-focus lateralization on the delta activity and the neuroimaging parameters. RESULTS: There was no significant difference in the amount of delta activity in the temporal lobe between the controls and patients. We found no correlation between delta activity and the neuroimaging measures (p>0.05). The ANOVA showed significant differences between the patients and controls for the volume of the gray and white matter of the temporal lobe and for the NAA in the lateral and posterior temporal lobe (p<0.002). CONCLUSIONS: The interictal background delta activity was not explained by reduced volume of the temporal lobe white matter, gray matter, or by abnormalities seen in 1H-MRSI.     

Standardization of amygdalohippocampectomy with intraoperative magnetic resonance imaging: preliminary experience

PURPOSE: Intraoperative magnetic resonance imaging (IMRI) is an extremely useful neurosurgical tool in surgeries in which the extent of resection is known to have a significant impact on outcome. Residual hippocampus is the most common cause of recurrent seizures after temporal lobectomy for medial temporal lobe epilepsy. Although the risk/benefit ratio of a policy of universal radical hippocampal resection is not known, we hypothesized that IMRI would aid in the intraoperative assessment of the extent of hippocampal resection and assist in accomplishing a complete hippocampectomy. METHODS: Five consecutive patients with medically intractable medial temporal lobe epilepsy underwent a radical amygdalohippocampectomy as part of the their surgery for epilepsy. IMRI was used before surgery and after an initial resection. The quality of images was assessed. Postoperative MR images were evaluated by a radiologist to determine the extent of resection of the amygdala, hippocampus, and parahippocampal gyrus. RESULTS: There were no perioperative infections. After a mean follow-up of 10 months, all patients are seizure free. T(1)-weighted coronal intraoperative images were judged adequate at visualizing the medial structures in all patients. T(2) and fluid-attenuated inversion recovery (FLAIR) images did not provide useful information. Postoperative MR images indicated that a complete hippocampectomy had been achieved in all patients. CONCLUSIONS: IMRI is a useful adjunct in the surgical treatment of medial temporal lobe epilepsy and perhaps the most reliable method of standardizing a complete hippocampectomy. T(1)-weighted coronal images are the most helpful sequence.     

A short-echo-time proton magnetic resonance spectroscopic imaging study of temporal lobe epilepsy

PURPOSE: We used short-echo-time proton magnetic resonance spectroscopy imaging (MRSI) to study metabolite concentration variation through the temporal lobe in patients with temporal lobe epilepsy (TLE) with and without abnormal MRI. METHODS: MRSI was performed at TE = 30 ms to study 10 control subjects, 10 patients with TLE and unilateral hippocampal sclerosis, and 10 patients with TLE and unremarkable MRI (MRI negative). We measured the concentrations of N-acetyl aspartate +N-acetyl aspartyl-glutamate (NAAt), creatine (Cr), choline (Cho), glutamate + glutamine (Glx), and myoinositol, in the anterior, middle, and posterior medial temporal lobe (MTL), and in the posterior lateral temporal lobe. Segmented volumetric T1-weighted MRIs gave the tissue composition of each MRSI voxel. Normal ranges were defined as the control mean +/- 3 SD. RESULTS: In the hippocampal sclerosis group, seven of 10 had abnormally low NAAt in the ipsilateral anterior MTL. In the MRI-negative group, four of 10 had low NAAt in the middle MTL voxel ipsilateral to seizure onset. Metabolite ratios were less sensitive to abnormality than was the NAAt concentration. Group analysis showed low NAAt, Cr, and Cho in the anterior MTL in hippocampal sclerosis. Glx was elevated in the anterior voxel contralateral to seizure onset in the MRI-negative group. Metabolite concentrations were influenced by voxel position and tissue composition. CONCLUSIONS: (a) Low NAAt, Cr, and Cho were features of the anterior sclerotic hippocampus, whereas low NAAt was observed in the MRI-negative group in the middle MTL region. The posterior temporal lobe regions were not associated with significant metabolite abnormality; (b) The two patient groups demonstrated different metabolite profiles across the temporal lobe, with elevated Glx a feature of the MRI-negative group; and (c) Voxel tissue composition and position influenced obtained metabolite concentrations.     

Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: Preliminary results

Purpose:   High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) and without (TLE-no) hippocampal sclerosis.
Methods:   High-resolution T₂-weighted hippocampal images were acquired in 34 controls: 15 TLE-MTS and 18 TLE-no. Entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, and CA3, and dentate (CA3&DG) volumes were determined using a manual parcellation scheme.
Results:   TLE-MTS had significantly smaller ipsilateral CA1, CA2, CA3&DG, and total hippocampal volume than controls or TLE-no. Mean ipsilateral CA1 and CA3&DG z-scores were significantly lower than ipsilateral CA2, ERC, and SUB z-scores. There were no significant differences between the various subfield or hippocampal z-scores on either the ipsi- or the contralateral side in TLE-no. Using a z-score ≤−2.0 to identify severe volume loss, the following atrophy patterns were found in TLE-MTS: CA1 atrophy, CA3&DG atrophy, CA1 and CA3&DG atrophy, and global hippocampal atrophy. Significant subfield atrophy was found in three TLE-no: contralateral SUB atrophy, bilateral CA3&DG atrophy, and ipsilateral ERC and SUB atrophy.
Discussion:   Using a manual parcellation scheme on 4 Tesla high-resolution MRI, we found the characteristic ipsilateral CA1 and CA3&DG atrophy described in TLE-MTS. Seventeen percent of the TLE-no had subfield atrophy despite normal total hippocampal volume. These findings indicate that high-resolution MRI and subfield volumetry provide superior information compared to standard hippocampal volumetry.     

Magnetic resonance imaging in the study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats

PURPOSE: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium-pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy. METHODS: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T(2)- and T(1)-weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks. RESULTS: At 2 h after status epilepticus (SE), a blood-brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T(2)-weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE. CONCLUSIONS: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.     

Combined measurements of hippocampal N-acetyl-aspartate and T2 relaxation time in the evaluation of mesial temporal lobe epilepsy: correlation with clinical severity and memory performances.

PURPOSE: In this study we tried to find a correlation between the clinical severity and memory performances, by comparing proton magnetic resonance (MR) spectroscopy and T2 relaxation time measurements in the hippocampi, in a homogeneous group of 27 patients with unilateral mesial temporal lobe epilepsy with ipsilateral hippocampal sclerosis on MR imaging, with a view to answer the following questions: (a) how sensitive is this approach for the assessment of the apparently normal contralateral hippocampus, (b) do the results relate to the clinical severity, and (c) does it allow evaluation of the degree of hippocampal dysfunction. METHODS: Volume-selective proton MR spectroscopy of the head of both hippocampi was performed at 3 T, by using the PRESS sequence, with an echo time of 135 ms, to estimate NAA/(Cho + Cr) ratios. The relaxation times were measured at 0.28 T, by using a conventional Carr-Purcell-Meiboom-Gill sequence, with a repetition time of 2,000 ms, an echo time of 15 ms, and 48 echoes. RESULTS: The combination of NAA/(Cho + Cr) ratio and T2 relaxation time values was allowed to classify contralateral hippocampus abnormalities in two groups: first, decreased NAA/(Cho + Cr) ratio with strongly increased T2 relaxation time values corresponding to abnormalities observed in sclerotic ipsilateral hippocampi; and second, decreased NAA/(Cho + Cr) ratio with normal or slightly increased T2 relaxation time values. Whereas the NAA/(Cho + Cr) ratio or T2 relaxation time value alone was not correlated with memory performances, their association shows that left hippocampal injury evaluated both by NAA and T2 relaxation time measurements was clearly correlated with verbal memory scores, and right hippocampal injury, with visual memory scores. On the other hand, the maximal seizure frequency reported by the patients was correlated with ipsilateral NAA/(Cho + Cr) ratio and T2 relaxation time values but not with contralateral results. CONCLUSIONS: We showed that the combination of NAA and T2 relaxation time measurements can be used to examine the degree of ipsi- and contralateral hippocampal dysfunction or injuries and their relations with memory performances in the presurgical evaluation of patients.     

Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy

Purpose: Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE. Methods: Three different MRI studies were performed involving 23 patients with unilateral MTLE (8 left and 15 right) and 34 healthy controls: (1) voxel‐based morphometry (VBM), (2) diffusion tensor imaging (DTI) and (3) probabilistic tractography (PT). VBM was employed to define differences in regional gray matter volume (GMV) between controls and patients. Voxel‐wise analyses of DTI evaluated differences in fractional anisotropy (FA), mean diffusivity (MD) and hippocampal PT. Z‐scores were computed for regions‐of‐interest (ROI) GMV and peri‐hippocampal FA and MD (to quantify hippocampal fiber integrity). The relationship between hippocampal deafferentation and regional GMV was investigated through the association between ROI Z scores and hippocampal fiber integrity. Results: Patients with MTLE exhibited a significant reduction in GMV and FA in perihippocampal and limbic areas. There was a decrease in hippocampal PT in patients with MTLE in limbic areas. A significant relationship between loss of hippocampal connections and regional GMV atrophy was found involving the putamen, pallidum, middle and inferior temporal areas, amygdala and ceberellar hemisphere. Discussion: There is a relationship between hippocampal disconnection and regional brain atrophy in MTLE. These results indicate that hippocampal deafferentation plays a contributory role in extrahippocampal brain damage in MTLE.     

Clinical patterns of patients with temporal lobe epilepsy and pure amygdalar atrophy

PURPOSE: MRI volumetric measurements (MRIvol) have been proven reliable in determining mesial temporal atrophy in patients with TLE. We attempted to correlate the clinical features with different patterns of hippocampal formation (HF) and amygdala (AM) atrophy in patients with TLE without foreign tissue lesion. METHODS: We studied 65 patients with refractory TLE. They were divided into five groups according to MRIvol results: pure AM atrophy (n = 11, 10 unilateral and one bilateral), unilateral HF atrophy (n = 16), bilateral HF atrophy (n = 12), unilateral AM + HF atrophy (n = 13), and patients with normal volumes of AM and HF (n = 13). MRIvol of AM and HF were performed by using a protocol previously described by Watson et al. (Neurology 1992;42:1743-50). RESULTS: Patients with AM atrophy had later onset of seizures compared with those with unilateral HF atrophy (p < 0.01). History of febrile convulsions (p < 0.0001) and frequent secondarily generalized tonic-clonic seizures (GTCSs) were more often found in patients with HF atrophy compared with those with pure AM atrophy and those with normal volumes (p = 0.04). Prolonged postictal confusion was more often found with AM atrophy (p = 0.05). Memory impairment was more severe in patients with HF atrophy than in those with AM atrophy only or in those with normal volumes (p = 0.03). There were no significant differences among the five groups in the following parameters: age, duration of epilepsy, seizure frequency, and presence and type of aura. CONCLUSIONS: Prolonged postictal confusion appeared to be related to AM atrophy, in keeping with previous clinical observations. These patients also had a lower incidence of early febrile convulsions, older age at epilepsy onset, lower frequency of secondary GTCS, and lesser memory dysfunction compared with patients with hippocampal atrophy.     

Diagnostic problems in “clinically definite” multiple sclerosis patients with normal CSF and multiple MRI abnormalities

Among patients who underwent cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) examination during a 5-year period, we found 18 patients at the multiple sclerosis center of the University of Rome and clinically definite multiple sclerosis, MRI white matter abnormalities, normal CSF examination, a disease duration of at least 1 year and an upper age of < 45 years at onset These patients were examined again with a variety of tests screening for different diseases mimicking multiple sclerosis. Alternative diagnoses reached after laboratory tests were: Lyme disease, two cases of vasculitis, mitochondrial encephalomyopathy, multiple ischemic lesions caused by atrial septum aneurysm and olivopontocerebellar atrophy. Hence, six of these 18 patients had a final diagnosis other than multiple sclerosis, while 12 remained with a final diagnosis of “MS with normal CSF”. Our study suggests that in patients with a clinical picture of multiple sclerosis and disseminated white matter MRI lesions but no CSF abnormalities, the classical clinical criteria may not be sufficiently specific, unless confirmed by a very prolonged clinical history with repeated MRI.     

Quantitative neuropathology of the entorhinal cortex region in patients with hippocampal sclerosis and temporal lobe epilepsy

PURPOSE: Clinical, radiologic, and experimental evidence indicates that the entorhinal cortex (EC) region may be linked to the pathophysiology of hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. Few neuropathologic studies of this region have been undertaken in patients with HS undergoing surgery, some suggesting preferential loss of layer III neurones. METHODS: We carried out a quantitative analysis in 26 patients with HS, nine patients with lesional temporal lobe epilepsy (LTLE), and eight postmortem controls. We measured neuronal densities in EC by using a three-dimensional cell-counting technique on NeuN immunostained and Nissl-stained sections. We also quantified the density of calretinin-positive interneurones in this region and the density of neurones in adjacent subiculum and CA1 subfields. We also assessed the patterns of gliosis in the EC in the patient groups and the presence of any neocortical neurone loss. RESULTS: No significant difference was found in the mean neuronal densities in the EC region between HS and LTLE groups or postmortem controls. Laminar gliosis in midcortical layers was seen in a proportion of HS cases but also in the LTLE group. No significant difference was seen in the density of calretinin interneurones and no correlation between the presence of neocortical neuronal loss and EC neuronal densities. CONCLUSIONS: A stereotypical pattern of neuronal loss and gliosis in the EC region in patients with HS is not confirmed that distinguishes this pathologic process from that in patients with lesional TLE.