Isolated amygdala enlargement in temporal lobe epilepsy: A systematic review

ObjectiveThe objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies.MethodsPubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords ‘amygdala enlargement’, ‘epilepsy’, and ‘seizures’ in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included.ResultsOf 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small samples of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2 years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67–100% vs. 26–47%), and they have an excellent response to antiepileptic drugs (81.8%–100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls.ConclusionsReliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests characteristics of an older age of epilepsy onset, a greater tendency to nonconvulsive seizures, and a good response to antiepileptic drugs in this interesting group of epilepsies.     

Clinical features and pathological characteristics of amygdala enlargement in mesial temporal lobe epilepsy

Although the hippocampus is considered an important site of seizures in mesial temporal lobe epilepsy (mTLE), the amygdala may also have a significant role. Amygdala enlargement is occasionally found in patients with mTLE, and volumetric detection of amygdala enlargement has been documented in "image-negative" patients with TLE. However, only limited data have been reported on the clinical features, surgical outcomes, and pathological characteristics in patients with mTLE with amygdala enlargement. We recruited 12 patients who had undergone surgical treatment for refractory epilepsy with radiological evidence of amygdala enlargement, and 11 became seizure free. All patients showed homogenously increased amygdala volumes on MRI without enhancement and underwent surgical treatment for mTLE. Pathology results revealed that eight patients had focal cortical dysplasia (FCD), two had ganglioglioma, one had oligodendroglioma, and one had astrocytoma. The clinical features and MRI findings were largely indistinguishable between the patients with brain tumors and those with FCD, but the patients with brain tumors tended to be younger at the time of seizure onset. Our study shows that surgical treatment of epilepsy in patients with amygdala enlargement usually has a favorable outcome. FCD was the most frequent pathological diagnosis in these patients. However, a brain tumor should be considered in the differential diagnosis, especially in young patients, because it is often difficult to differentiate FCD from a brain tumor on radiological features.     

非病灶性药物难治性颞叶癫痫的致痫源定位与显微外科手术治疗

目的探讨非病灶性颞叶癫痫致痫源的定位并分析其显微外科手术治疗结果。方法收治的25例患者经临床表现、脑电图（EEG）／动态脑电图（VEEG）、MRI海马相、单光子发射断层扫描（SPECT）和正电子发射断层扫描（PET）检查诊断为非病灶性颞叶癫痫，均正规服用药物2年以上，但癫痫发作症状均未有效地控制。其中18例行标准前颞叶及海马杏仁核切除术，7例行选择性海马杏仁核切除术。结果随诊观察7～53个月，按照Engel术后疗效分级标准：Ⅰ级17例，Ⅱ级2例，Ⅲ级5例，Ⅳ级1例。结论致痫源的准确定位并采用显微外科技术可以提高手术疗效，减少并发症。     

Diagnosis and treatment of temporal lobe epilepsy

Of the 1,200,000 Americans with partial epilepsy, temporal lobe epilepsy (TLE) occurs in more than 400,000. Temporal lobe seizures are usually stereotypic in their symptoms and duration. A typical sequence is an aura followed by arrest of motor behavior, blank stare, and automatisms. Patients with TLE often show impairments in attention, memory, mental processing speed, executive functions, mood, personality, and drive-related behaviors. Interictal depression occurs in approximately one third of TLE patients. TLE is diagnosed by a history of characteristic partial seizure symptoms. The diagnosis is confirmed by the capture of a typical episode during an electroencephalogram (EEG) or video-EEG, with epileptiform activity over one or both temporal regions. Video-EEG monitoring has revolutionized diagnosis and should be considered in patients in whom diagnosis is uncertain. TLE is treated with medications, resective surgery, and vagus nerve stimulation. Epilepsy surgery should be considered in all patients with refractory partial epilepsy.     

The epileptogenic zone in pharmaco‐resistant temporal lobe epilepsy with amygdala enlargement

Aims. Temporal lobe epilepsy with amygdala enlargement (TLE‐AE) has been considered a subtype of TLE. We evaluated the epileptogenic zone in patients with TLE‐AE, who underwent intracranial video‐EEG (ivEEG) and/or intraoperative electrocorticography (ioECoG) as well as epilepsy surgery. Methods. Eleven patients with TLE‐AE were enrolled and investigated based on seizure profile, volumetric MRI, the Wechsler Memory Scale‐Revised (WMS‐R), the location of seizure onset zone (SOZ) and irritative zone (IZ) based on ivEEG (n=8), the location of interictal epileptiform discharges (IEDs) based on ioECoG (11), surgical procedure, and seizure outcome. Results. The mean age at seizure onset was 34.9 years (range: 23–57). The mean duration of seizures was 5.0 years (range: 1–10). The number of AEDs was 2.3 (range: 1–5). The mean seizure frequency was nine per month (range: 1–30/month). All patients presented with focal impaired awareness seizures with (n=9) and without (2) secondary generalized convulsions. Volumetric MRI analysis showed unilateral enlarged amygdala with statistical significance (p<0.01). None of the patients' hippocampi had any abnormality based on MRI. Pre‐operative mean verbal, visual, and delayed recall scores based on the WMS‐R were over 100. The SOZ and IZ were identified in both the amygdala and hippocampus in seven patients and in only the amygdala in one patient based on ivEEG. IEDs were identified in the hippocampus in six patients and in both the amygdala and hippocampus in four patients based on ioECoG. All 11 patients underwent anterior temporal lobectomy, including amygdala resection, with multiple hippocampal transections (dominant hemisphere: seven patients) and resection (non‐dominant hemisphere: three patients). Nine (81.8%) of 11 patients achieved seizure freedom with a mean follow‐up of 26 months (range: 12–47). Post‐operative WMS‐R results did not show any significant deterioration, with a mean follow‐up of 15 months (range: 12–24). The resected amygdala showed no histopathological abnormality. Conclusion. The epileptogenic zone of TLE‐AE involves both the amygdala and hippocampus. ivEEG may be needed to explore the SOZ in normal hippocampus in addition to enlarged amygdala. Amygdala resection and multiple hippocampal transections may control the epileptogenic limbic system and save memory function in patients with TLE‐AE.     

Alterations in functional connectivity of the amygdala in unilateral mesial temporal lobe epilepsy

The aim of this work was to evaluate the relationship between ipsilateral amygdala dysfunction in unilateral mesial temporal lobe epilepsy (MTLE) and remote temporal, frontal, and parietal brain structures and to identify their association with theory of mind (ToM) abilities. Functional magnetic resonance imaging (fMRI) data were acquired from MTLE patients with unilateral hippocampal sclerosis (n?=?28; 16 left-sided) and healthy controls (HC, n?=?18) watching an animated fearful face paradigm. To explore functional connectivity, we used independent component analysis (ICA) of fMRI data to characterize possible amygdala network alterations that may be caused by lateralized amygdala dysfunction. We furthermore investigated the relationship between activation within the amygdala network and ToM task performance. The pattern of amygdalar BOLD activation observed in response to an animated fearful face paradigm was bilateral amygdalar activation in HC and amygdala activation lateralized to the contralateral side in MTLE patients. In HC, a hemispheric asymmetry of the amygdala network was present with amygdala co-activation in predominantly left temporolateral and frontal brain structures. In MTLE patients, the observed asymmetry of amygdala connectivity was modulated by the side of pathology and the extent of amygdalar connectivity to the parahippocampal gyrus and insula was related to ToM test performance. These findings suggest that ipsilateral amygdalar dysfunction in MTLE is associated with alterations in remote temporal and frontal brain areas. The study of psychiatric and neurological disorders via network analysis allows for a shift of focus away from viewing dysfunctions of individual structures to a pathological network that possibly gives rise to a variety of symptoms.     

颞叶癫痫的外科治疗进展

癫痫是由多种原因导致的脑部神经元异常放电,引起机体运动?感觉?意识?行为和自主神经的不同程度障碍,其临床表现具有发作性?短暂性?重复性和刻板性的特点.颞叶癫痫(Temporal Lobe Epilepsy)是一种难治性部分癫痫,早期手术治疗疗效优于抗癫痫药物(AEDs)治疗[1-3],手术治愈率为60%~80%,有效率高达85%[4].随着现代医学影像技术的快速发展及颅内电极脑电图检测的广泛临床应用,颞叶癫痫的致痫灶定位更加精确,外科手术疗效得到广泛的认可.     

High and low frequency electrical stimulation in non-lesional temporal lobe epilepsy

In patients with pharmacologically intractable epilepsy who are not eligible for surgery, deep brain stimulation is currently under evaluation as an alternative treatment. Optimal stimulation parameters, including high (HFS) versus low frequency (LFS) stimulation, are not well defined. Here, we report the effects of HFS (130 pulses per second, pps) and LFS (5pps) of the principal epileptogenic focus, in three patients with non-lesional temporal lobe epilepsy. HFS, but not LFS, was associated with a reduction of the interictal discharges and absence of seizures. HFS may be beneficial in patients with non-lesional temporal lobe epilepsy who are not surgical candidates.     

Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Marked accumulation of oligodendroglia‐like cells in temporal lobe epilepsy with amygdala enlargement and hippocampal sclerosis

Although an increasing number of cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have been reported, there are few pathological reports, and no clear consensus has been established. Oligodendroglia or oligodendroglia‐like cells (OLCs) have recently attracted attention in epilepsy studies. Here, we report the clinical and pathological findings of a 40‐year‐old male TLE patient with AE and hippocampal sclerosis, in whom histopathological study demonstrated remarkable clustering of OLCs around the uncus. The patient began to have refractory seizures at the age of 14, and preoperative MRI revealed left amygdala enlargement and left hippocampal atrophy. Other examinations were consistent with left mesial temporal epileptogenicity. He underwent surgical resection and achieved seizure freedom. Histopathological study of the amygdala showed swollen neurons with relatively large bodies and thick neurites, accompanied by vacuolar degeneration in the background. Additionally, there were marked clusters of OLCs with round nuclei and densely stained chromatin around the uncus. The OLCs were Olig2‐positive. In the hippocampus, severe cell loss in CA1 and granule cell dispersion in the dentate gyrus were found. These findings may provide some insights for further pathological investigations of TLE with non‐neoplastic AE.     

磁共振表现为一侧海马硬化的颞叶癫痫手术治疗长期随访结果

目的：探讨磁共振表现为一侧海马硬化的颞叶癫痫手术治疗长期疗效。方法对25例磁共振表现为一侧海马硬化的药物难治性颞叶癫痫患者,在术中脑电监测下行裁剪式前颞叶切除术,术后长期随访,评估癫痫控制效果。结果术后疗效良好,癫痫控制效果按ILAE分类法,术后1年76％患者达1级,4％为2级,16％为3级,4％为5级;术后3年68％为1级,4％为2级,24％为3级,4％为5级;术后5年65％为1级,29％为3级,6％为5级。结论手术治疗磁共振表现为一侧海马硬化颞叶癫痫长期疗效满意,患者生活质量改善。     

Recognition of emotion with temporal lobe epilepsy and asymmetrical amygdala damage

PURPOSE: Impairments in emotion recognition occur when there is bilateral damage to the amygdala. In this study, ability to recognize auditory and visual expressions of emotion was investigated in people with asymmetrical amygdala damage (AAD) and temporal lobe epilepsy (TLE). METHODS: Recognition of five emotions was tested across three participant groups: those with right AAD and TLE, those with left AAD and TLE, and a comparison group. Four tasks were administered: recognition of emotion from facial expressions, sentences describing emotion-laden situations, nonverbal sounds, and prosody. RESULTS: Accuracy scores for each task and emotion were analysed, and no consistent overall effect of AAD on emotion recognition was found. However, some individual participants with AAD were significantly impaired at recognizing emotions, in both auditory and visual domains. CONCLUSIONS: The findings indicate that a minority of individuals with AAD have impairments in emotion recognition, but no evidence of specific impairments (e.g., visual or auditory) was found.     

Mood state in unilateral temporal lobe epilepsy

The purpose of this investigation was to reexamine the relationship between self-reported depression and laterality of temporal lobe epilepsy and to determine the contribution of associated frontal lobe dysfunction in predisposing patients to depression. Sixty-four patients with complex partial seizures of left (n = 26) or right (n = 38) temporal lobe origin were administered several self-report measures of mood state (Beck Depression Inventory, Center for Epidemiological Studies-Depression scale, Beck Anxiety Inventory), and a test of frontal lobe function [Wisconsin Card Sorting Test (WCST)]. There were no overall differences between the left and right temporal lobe groups on the measures of depression and anxiety. However, the left temporal lobe group exhibited a significant relationship between the degree of associated frontal lobe dysfunction (as indicated by increased perseverative responding on the WCST) and dysphoric mood state. For the right temporal lobe group there was a nonsignificant inverse relationship between mood state and indices of frontal lobe dysfunction. These results (1) are consistent with the broader psychiatric literature, which has implicated a relationship between depression and left frontal lobe dysfunction, (2) suggest that previous conflicting reports of depression/left temporal lobe epilepsy relationship are due in part to variations in the intactness of frontal lobe function, and (3) suggest that the presence of associated frontal lobe dysfunction may be a consideration in understanding interictal psychopathology in epilepsy.