Accelerated long-term forgetting in temporal lobe but not idiopathic generalised epilepsy

Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF), in which memories are retained normally over short delays but are then lost at an accelerated rate over days or weeks. The causes of ALF, and whether it represents a consolidation deficit distinct from the one associated with forgetting over short delays, remain unclear. In addition, methodological issues have made results of some previous studies difficult to interpret. This study used improved methodology to investigate the role of seizure activity in ALF. Forgetting was assessed in participants with TLE (who have involvement of temporal lobe structures) and idiopathic generalised epilepsy (IGE; in which seizures occur in the absence of identified structural pathology in the temporal lobes). Learning of novel stimuli was matched between patients with TLE, patients with IGE and healthy controls matched for age and IQ. Results indicated that the TLE group showed accelerated forgetting between 30-min and three-weeks, but not between 40-s and 30-min. In contrast, rates of forgetting did not differ between patients with IGE and controls. We conclude that (1) ALF can be demonstrated in TLE in the absence of methodological confounds; (2) ALF is unlikely to be related to the experience of epilepsy that does not involve the temporal lobes; (3) neither seizures during the three-week delay nor polytherapy was associated with ALF.     

Accelerated long-term forgetting in temporal lobe epilepsy: evidence of improvement after left temporal pole lobectomy

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls.     

经颞下回-侧脑室入路选择性海马杏仁核切除术治疗内侧颞叶癫痫

目的 探讨经颞下回-侧脑室入路选择性海马杏仁核切除术治疗内侧颞叶癫痫的手术方法 、疗效及并发症. 方法 对确诊为药物难治性内侧颞叶癫痫的62例患者,经颞部锁孔开颅,切除中前段颞下回,进入颞角前外侧区,选择性切除海马杏仁核及海马旁回等内侧颞叶结构.结果 62例患者术后随访至少24～80个月,无严重手术并发症;Engel癫痫疗效分级;Ⅰ级45例(72.6%),Ⅱ级12例(19.4%),Ⅲ级5例(8.0%). 结论 经颢下回-侧脑室入路选择性海马杏仁核切除术是治疗内侧颞叶癫痫的有效方法 ,其手术创伤小,可妥善保护语言区和视放射,安全性高.     

When “long-term memory” no longer means “forever”: Analysis of accelerated long-term forgetting in a patient with temporal lobe epilepsy

Classical amnesia involves a difficulty in transferring information to long-term memory and can be detected with standard clinical tests. However, there are some patients who pass these tests but nonetheless show longer-term memory impairments. A case study is presented of a patient, RY, with temporal lobe epilepsy, who exhibited such a profile of “accelerated long-term forgetting”. To investigate the effect of recalling information on later retention, recall and recognition for pairs of novel stories were tested at five intervals ranging from 30 min to 4 weeks; we also manipulated whether or not recall and recognition were repeatedly tested for stories. Two studies are reported, one before RY commenced treatment with anticonvulsant medication, and one following 6 months of treatment. Very similar memory profiles were observed in both settings. Against a background of above average cognitive function, results showed that RY's free recall, although initially average or above, was significantly impaired at extended delays (within 24 h) for non-repeatedly recalled episodic information. However, this contrasted with normal performance for information that had been repeatedly recalled. An unresolved issue in the field is the impact of anticonvulsant medication on alleviating long-term forgetting, and the current study shows that anticonvulsant medication can have negligible beneficial effects in improving the rate of long-term forgetting in this type of patient. In addition, our study highlights the possible protective effect of active review of recent episodic memories.     

神经导航下锁孔入路选择性海马杏仁核切除术治疗内侧颞叶癫痫

目的 探讨神经导航下锁孔入路选择性海马杏仁核切除术治疗顽固性内侧颞叶癫痫的可行性.方法 总结分析18例神经导航下锁孔入路选择性海马杏仁核切除病例,所有病例均经过临床特征、影像检查、视频脑电监测、脑磁图检查确定为顽固性内侧颞叶癫痫.结果 随访结果显示72.2%病例术后癫痫发作停止.Engel癫痫疗效分级:Ⅰ级72.2%,Ⅱ级22.2%,Ⅲ级5.6%.结论 神经导航下锁孔入路选择性海马杏仁核切除术是一种安全可行的手术方法,疗效满意.     

Verbal learning and forgetting in patients with temporal lobe epilepsy

Studies comparing non-surgical patients with left or right temporal lobe epilepsy (TLE) have shown irregular differences in verbal learning and memory. We assessed the performance of unoperated patients with epileptogenic temporal lobe lesions or cryptogenic TLE using a selective reminding procedure for the learning of a word list, and five delayed trials for the recall of learned words. On the selective reminding procedure, patients with left TLE were found to be more impaired than those with right TLE and controls, in agreement with the role of the left temporal lobe in verbal learning. The patients with right TLE were more impaired than the controls, possibly due to the semantic organization of the word list The rate of forgetting learned words was similar in the patient and control groups, suggesting that patients with left TLE can normally retain and/or retrieve stored items. These data support the hypothesis that distinct functional systems subserve learning and memory. Comparisons of the patient subgroups with epileptogenic lesions (hippocampal sclerosis or low-grade glioma) and those with cryptogenic TLE did not reveal any significant difference in learning or in memory, suggesting that epileptiform activity could affect verbal performance as a detectable temporal lesion.     

Mortality after temporal lobe epilepsy surgery

Purpose: To report mortality, after a longer interval, in a cohort of patients with drug‐resistant epilepsy treated by temporal lobe surgery between 1975 and 1995. A previous audit of these patients ending December 1, 1997 observed a standardized mortality ratio (SMR) of 4.5. Methods: We analyzed mortality in a cohort of 306 patients with temporal lobe epilepsy (TLE) who underwent temporal lobe resections between December 1, 1975 and December 1, 1995. Deaths occurring after December 1,1997 and until December 1, 2009 were evaluated. Medical records, death certificates, postmortem examination reports, coroner officer’s reports, and coroner’s inquest reports were sought, and causes of death were ascertained. Sudden unexpected death in epilepsy (SUDEP) cases were identified. Key Findings: In 3,569 person‐years of follow‐up 19 deaths occurred, [SMR 2.00, 95% confidence interval (CI) 1.27–3.13], 14 men (SMR 2.01, 95% CI 1.19–3.39) and 5 women (SMR 1.68, 95% CI 0.70–4.03). On analysis of subgroups, SMRs were significantly elevated in patients with mesial temporal sclerosis (MTS) (SMR 2.50, 95% CI 1.38–4.51), men with MTS (SMR 3.12, 95% CI 1.56–6.25), men with nonspecific lesions (SMR 2.68, 95% CI 1.00–7.09), and right‐sided resections in MTS (SMR 3.33, 95% CI 1.39–8.00). During follow‐up, six SUDEP cases were observed with a rate of 1/595 person‐years. Significance: In this cohort, the risk for premature death in patients undergoing TLE surgery decreased over time but remained above the standard population. Men had a slightly higher risk than women, as did right‐sided resections in MTS, confirming this observation in the original cohort. Although lower, the risk of SUDEP remained. Without up‐to‐date information on seizure outcome, we were unable to directly relate this to mortality.     

Mitochondrial involvement in temporal lobe epilepsy

Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca²⁺ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.     

Depression in temporal lobe epilepsy surgery patients: an FDG-PET study

PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. METHODS: We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p<0.001 for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.     

侧裂入路选择性海马、杏仁核切除术治疗颞叶癫癎

目的总结对颞叶癫病人行侧裂径路选择性海马、杏仁核显微切除术的经验。方法对28例顽固性颞叶癫病人进行常规脑电图(蝶骨电极)、视频脑电图实时监测、MRI、单光子发射断层显像(SPECT)、正电子发射断层成像(PET)等检查,确定颞叶癫灶。行翼点开颅,经右侧手术17例,左侧11例,行颞叶径路选择性海马、杏仁核显微切除术。结果术后发作完全停止20例(71.4%);症状显著改善,偶有发作3例(10.7%);好转3例(10.7%);无效2例。结论根据临床表现及综合性辅助检查确定颞叶癫,行侧裂径路选择性海马、杏仁核显微切除术,可以取得满意疗效;但要求解剖清晰,显微外科技术熟练,避免意外损伤脉络膜前动脉和大脑中动脉。     

手术治疗颞叶癫痫的远期疗效及影响因素分析

目的探讨手术治疗颞叶癫痫的远期疗效及影响因素。方法皮层电极及深部电极引导下手术治疗59例颞叶癫痫,其中前颞叶＋海马杏仁核切除术57例,选择性海马杏仁核切除术2例。术后进行长期追踪术后随访6-16年,回顾性研究影响患者预后的因素。结果癫痫控制满意44例,显著改善6例,良好3例,无效6例,有效率89.8%。其中癫痫完全消失36例,占61%。复发4例,无死亡病例,记忆力减退3例,精神症状2例。结论手术治疗颞叶癫痫安全有效,但存在远期复发的可能;少数患者远期可能出现记忆力减退及精神症状等;疗效与病例的选择及致癫灶的准确定位等因素有关。     

Age-dependent seizure semiology in temporal lobe epilepsy

OBJECTIVE: To examine the effects of age on different aspects of temporal lobe seizure semiology. METHODS: We performed a video analysis of 605 archived seizures from 155 consecutive patients (age 10 months to 49 years) selected by seizure freedom after temporal lobectomy. Eighty patients had hippocampal sclerosis (HS). Beside semiological seizure classification, we assessed age dependency of several axes of seizure semiology: (1) aura, (2) number of different lateralizing signs, occurrence of ictal (3) emotional signs, (4) autonomic symptoms, (5) automatisms, and (6) secondary generalization as well as (7) the ratio of motor seizure components. RESULTS: From the 155 patients, 117 reported aura, 39 had ictal emotional signs, 51 had autonomic symptoms, 130 presented automatisms, while 18 patients showed secondary generalization at least once during their seizures. Altogether 369 (median: 2/patient) different lateralizing signs were recorded. Frequency of HS (p < 0.001), ictal automatisms (p < 0.001), secondary generalization (p = 0.014), number of different lateralizing signs (p < 0.001) increased while the ratio of motor seizure component (p = 0.007) decreased by age. Auras, emotional symptoms, and autonomic signs occurred independently of patients' ages. Hippocampal sclerosis adjusted linear models revealed that the frequency of automatisms and secondarily generalized seizures as well as the number of different lateralizing signs are HS-independent significant variables. CONCLUSION: Our findings support that brain maturation significantly influences the evolution of some important aspects (motor seizures, lateralizing signs) of temporal lobe seizure semiology. Conversely, other aspects (aura, emotional, and autonomic signs) are independent of the maturation process. This is the first report investigating age dependency of epileptic seizure semiology comparing all age groups.     

Depression in temporal lobe epilepsy before epilepsy surgery

PURPOSE: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. RESULTS: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.     

Accelerated long‐term forgetting in children with idiopathic generalized epilepsy

Purpose: The rapid forgetting of information over long (but not short) delays (accelerated long‐term forgetting [ALF]) has been associated with temporal lobe epilepsy but not idiopathic generalized epilepsy (IGE). Long‐term memory formation (consolidation) is thought to demand an interaction between medial temporal and neocortical networks, which could be disrupted by epilepsy/seizures themselves. The present study investigates whether ALF is present in children with IGE and whether it relates to epilepsy severity. Methods: Sixty‐one children (20 with IGE and 41 healthy controls [HC]) of comparable age, sex, and parental socioeconomic status completed neuropsychological tests, including a measure of verbal learning and recall after, short (30‐min) and long (7‐day) delays, and recognition. Epilepsy severity was rated by treating neurologists. Key Findings: A two‐way repeated measures analysis of covariance (ANCOVA) found a significant Group x Delay interaction; the children with IGE recalled (and recognized) significantly fewer words after a long, but not short (2‐ and 30‐min) delay relative to the HC children. Moreover, greater epilepsy severity was associated with poorer recognition. Significance: This study demonstrates, to our knowledge for the first time, that children with IGE present with ALF, which is related to epilepsy severity. These findings support the notion that epilepsy/seizures themselves may disrupt long‐term memory consolidation, which interferes with day‐to‐day functioning of children with IGE.     

Diffusion tensor analysis of temporal and extra-temporal lobe tracts in temporal lobe epilepsy

OBJECTIVE: To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties. METHODS: Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined. RESULTS: All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere. CONCLUSION: Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.     

Temporal lobe volumetric cell densities in temporal lobe epilepsy

Volumetric cell densities in 13 different subfields of the temporal lobe were calculated to test various hypotheses about mesial and lateral temporal lobe sclerosis in patients with complex partial epilepsy. In patients benefitting (primary group) from anterior temporal lobectomy (ATL), sclerosis was greater (fewer cells) in anterior than in posterior hippocampus. By contrast, the patients lacking full benefit (nonprimary group) from ATL had decreased numbers of neurons equally distributed from anterior to posterior hippocampus, indicating that zones of mesial temporal cell loss are linked to zones of epileptogenicity. These data support a model of focal hippocampal epilepsy originating from zones of cell loss and synaptic reorganization that is epileptic. There were no differences in cell densities in gyrus hippocampi or in lateral temporal gyri when patients with temporal lobe epilepsy and controls were compared. Hippocampal cell densities in mesial temporal lobe were not reduced in psychomotor epileptic patients with extrahippocampal foci consisting of foreign tissue. Variables in seizure histories were not correlated with Ammon's horn cell densities, indicating that most of the sclerosis preceded the seizures, which did virtually no significant further damage to hippocampus with repeated partial or generalized seizures.     

伽玛刀治疗颞叶癫痫的长期随访

目的 探讨颞叶癫痫的伽玛刀治疗的疗效。方法 用PET、SPECT、MRI、EEG检查痫灶位置，应用瑞典ELEKTA公司伽玛刀治疗系统行杏仁核毁损术(90～100Gy)加颞叶内侧或外侧低剂量(中心20Gy，边缘10Gy)伽玛射线照射38例。结果 本组38例经伽玛刀治疗后随访5．1～7．2年，满意26例，显著改善及良好各3例，无效6例，有效率84．2％。其中癫痫完全消失23例，占61％；1例3个月后出现精神症状，经激素、甘露醇治疗第六个月后症状消失；6例(在满意26例中)2年后癫病症状同治疗前。无病残及死亡。结论 伽玛刀行杏仁核毁损术加颞叶内侧或外侧低剂量照射，对颞叶癫痫具有明确的疗效，并发症少见。部分病例的复发可能与杏仁核毁损剂量不足有关。     

Hypersalivation in temporal lobe epilepsy

PURPOSE: We sought to determine whether hypersalivation helps lateralize seizure onset during complex partial seizures of temporal lobe origin. Several clinical signs, which help lateralize seizure onset, have been reported in temporal lobe epilepsy (TLE). Increased salivation only occasionally has been reported as a manifestation of partial epilepsy. METHODS: Of 590 consecutive patients admitted for video-EEG monitoring, either as a part of a presurgical evaluation of medically intractable epilepsy or for diagnosis and clarification of their paroxysmal symptoms, we identified 10 patients with ictal hypersalivation as a prominent manifestation of complex partial seizures. We reviewed the clinical features, scalp-sphenoidal video-EEG monitoring, intracarotid amytal (Wada) testing, hippocampal volumetric magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of these patients. RESULTS: Of the 10 patients with ictal hypersalivation, seven patients had nondominant/right TLE, and three patients had dominant/left TLE. All patients had hippocampal atrophy on volumetric MRI. Eight of the 10 patients underwent standard temporal lobectomy with amygdalohippocampectomy (six right, two left). All of the operated-on patients had a seizure-free (Engel class I) outcome, and their increased salivation resolved. Two patients, who did not undergo surgical treatment, continue to have complex partial seizures with increased salivation. CONCLUSIONS: We conclude that increased salivation as a prominent ictal finding in complex partial seizures of temporal lobe origin is more likely to be of nondominant temporal lobe origin. Further studies with larger numbers of patients are needed to replicate this finding.     

Gamma knife surgery for mesial temporal lobe epilepsy

PURPOSE: Gamma knife radiosurgery (GK) allows precise and complete destruction of chosen target structures containing healthy and/or pathologic cells, without significant concomitant or late radiation damage to adjacent tissues. All the well-documented radiosurgery of epilepsy cases are epilepsies associated with tumors or arteriovenous malformations (AVMs). Results prompted the idea to test radiosurgery as a new way of treating epilepsy without space-occupying lesions. METHODS: To evaluate this new method, we selected seven patients with drug-resistant "mesial temporal lobe epilepsy" (MTLE).The preoperative evaluation program was the one we usually perform for patients selected for microsurgery of TLE [video-EEG analysis of seizures, foramen ovale electrode recording, magnetic resonance imaging (MRI) positron emission tomography (PET) scan, neuropsychological testing]. In lieu of microsurgery, the amygdalohippocampectomy was performed by using GK radiosurgery. RESULTS: Morphologic (MRI) signs of destruction of the target took place at 9 months after GK surgery. Since the treatment day, the first patient has been seizure free. Seizure improvement came more gradually for the following patients, and complete cessation of seizures occurred around the tenth month (range, 8-15 months). MRI shows that the amygdaloentorhinohippocampal target was selectively injured. No significant side effect (except one case of homologous quadrantanopia) or morbidity and no mortality was observed. The current follow-up is 24-61 months, and all (but one) patients are seizure free. CONCLUSIONS: This initial experience proves clearly the short-to middle-term efficiency and safety of GK for MTLE surgery. These results need further confirmation of long-term efficiency, but the introduction of GK surgery into epilepsy surgery can reduce dramatically its invasiveness and morbidity.