ReviewIsolated amygdala enlargement in temporal lobe epilepsy: A systematic review
Introduction
The most common lesions identified in focal epilepsy are hippocampal sclerosis (40%), long-term epilepsy-associated tumors (27%), and malformations of cortical development (13%) [1]. Historically, the most common form of focal epilepsy, mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), has received the widest surgical attention. Hippocampal sclerosis can be reliably detected on routine magnetic resonance imaging (MRI) studies and is well-known for its epileptogenicity [2]. Mesial TLE due to HS is often medically resistant, and surgical resection can achieve up to 70% long-term seizure freedom in patients [3].
With improved neuroimaging and correlative presurgical techniques, clinicians are becoming increasingly aware of other potentially epileptogenic temporal lobe lesions that may also have good surgical outcome [4], [5]. While seizures originating from these other causes might have been classified as ‘nonlesional’ or ‘imaging-negative’ epilepsy previously, a greater awareness of other potentially epileptogenic lesions, as well as improved imaging technology, has resulted in the identification of enlarged amygdalae in a proportion of patients (see Fig. 1).
Bower et al. retrospectively found that 64% of ‘imaging-negative’ cases had both significant amygdala asymmetry and amygdala enlargement (AE), while Coan et al. demonstrated significant AE in 12% of previously diagnosed patients with ‘nonlesional’ TLE [4], [6]. Because nonlesional TLE may be associated with an almost three times lower probability of seizure freedom after surgical resection compared with lesional TLE, this reclassification of newly identified AE lesions in TLE has important implications for patient management [7].
Using parcellation based on cytoarchitecture, Murphy et al. showed in 1987 that the amygdaloid complex is asymmetric in humans, while in 1992, Watson et al. attempted to establish standardized anatomical guidelines for outlining the hippocampus and amygdala on high-resolution MRI scans [8], [9]. Although the technology has been available to measure amygdala volumes specifically since the early 1990s, studies linking amygdala pathology and size to seizure foci until recently have been lacking [8], [9].
There are a number of clinical, electroencephalographic, radiological, and histopathological observations that have led to an increased focus on the role of the amygdala independent from HS in epilepsy in recent years. Firstly, better outcomes have been observed when the amygdala was included in surgical resection borders [10]. Secondly, studies utilizing MRI T2 relaxometry have shown that a portion of patients with ‘imaging-negative’ TLE have increased T2 signal in the amygdala ipsilateral to the focus detected by electroencephalography (EEG) [11]. Thirdly, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) findings of glucose hypometabolism have been isolated to the amygdala and excluding the hippocampus in some patients [12]. Finally, histopathologic abnormalities have been found in amygdala specimens resected from patients with medically resistant TLE [13].
This review pools studies on TLE and AE to provide better understanding of this imperfectly described focal epilepsy syndrome. Specific focus will be on the seizure characteristics, diagnostic investigations, treatment outcomes, and histopathological results in these cohorts of patients. We aimed to identify knowledge gaps in the literature that can guide future clinical management and research.
Section snippets
Methods
Our search strategy comprised a comprehensive literature search of PubMed, Embase, and the Cochrane Library, conducted using the terms ‘amygdala enlargement’, ‘epilepsy’, and ‘seizures’, either alone or in varying combinations in April 2015. Papers were excluded for the following reasons: animal studies, irrelevant topics, non-English papers, papers not involving a population with epilepsy, case reports, and those described with coexisting brain pathology. The references of included papers were
Results
Our search strategy in April 2015 ultimately yielded 14 papers from seven countries published between 1999 and September 2014. Although three abstracts presented only at scientific meetings were unavailable for full review, for reference, they have been included in the tables of the Results section [15], [16], [17]. Three papers focusing only on psychiatric domains of TLE and AE cannot be directly compared with the other eight papers focusing on epilepsy and were not formally reviewed but were
Discussion
Methodological issues limit comparisons between studies on isolated amygdala enlargement in temporal lobe epilepsy. Population cohorts are relatively small and ascertained through mixed surgical or medical sources with varying control group comparisons. However, the key methodological issue remains the varying identification techniques for amygdala enlargement from automated software (voxel-based morphometry or FreeSurfer), to manual tracing techniques to visual inspection by blinded or
Conclusions
This review on isolated AE in epilepsy included eight key papers and, in total, 107 unique patients. Most papers provide reasonable evidence of the enlarged amygdalae as the epileptic focus and provide consistent syndrome characteristics with a later age of onset, more CPS compared with CS, and a high likelihood of being responsive to AED treatment.
Overall, however, sample sizes were small, suggesting that caution should be applied when attempting to draw conclusions with regard to patients
Disclosure of conflict of interest
Wendyl D'Souza has received travel, investigator-related, speaker honoraria and has served on a scientific advisory board from UCB Pharma; educational grants from Novartis Pharmaceuticals, Pfizer Pharmaceuticals and Sanofi–Synthelabo; educational, travel, and fellowship grants from GSK Neurology Australia; has served on scientific advisory boards and received honoraria from SciGen Pharmaceuticals. His department has received research funding from GlaxoSmithKline, SciGen, Pfizer, Novartis, and
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Anatomo-electro-clinical correlations of hypermotor seizures with amygdala enlargement: Hippocampal seizure origin identified using stereoelectroencephalography
2019, Epilepsy and Behavior Case ReportsCitation Excerpt :Reports of surgical and pathological findings of MTLE with AE are scarce. This not only is likely because this condition is generally well controlled with anticonvulsants [15], but also could be because ictal manifestation is difficult to differentiate from emotional disorders; therefore, it is not common that these cases reach surgical treatment [8]. The pathological findings reported are various, and in recent years, the pathological findings of AE have been considered to be heterogeneous [8,16,17].
Improvement in anti-N-methyl-D-aspartate receptor antibody-mediated temporal lobe epilepsy with amygdala enlargement without immunotherapy
2018, Epilepsy and Behavior Case ReportsCitation Excerpt :Therefore, we believe that our patient presented with a milder form or “forme fruste” of anti-NMDAR encephalitis. To date, a few reports have indicated that voltage-gated potassium channel (VGKC)-complex or glutamic acid decarboxylase (GAD) antibodies are among the pathophysiological factors underlying autoimmune TLE-AE [1,3]. No previous reports have demonstrated the presence of anti-NMDAR antibodies in TLE-AE; to the best of our knowledge, this is the first case report indicating that anti-NMDAR antibody-mediated processes may be associated with TLE-AE.