Abnormal behavior in children with temporal lobe epilepsy and ganglioglioma

Temporal lobe epilepsy in childhood is characterized by great clinical, electroencephalographic, and etiological diversity. The prognosis after temporal lobe epilepsy surgery in childhood is usually good, with most patients achieving complete seizure control. However, in some children behavior deteriorates postoperatively. We report two girls (2 and 6 years of age) with refractory seizures due to temporal lobe ganglioglioma. They exhibited aggression and hyperactivity since the beginning of their epilepsy. In both patients, behavioral disturbances worsened postoperatively, despite complete seizure control. Patients and parents should be advised about possible behavioral disturbances after epilepsy surgery, especially in the presence of a temporal lobe developmental tumor, even when seizure control is achieved postoperatively.     

The early identification of candidates for epilepsy surgery

The effectiveness of resective surgery for the treatment of carefully selected patients with medically intractable, localization-related epilepsy is clear. Seizure-free rates following temporal lobectomy are consistently 65% to 70% in adults and 68% to 78% in children. Extratemporal resections less commonly lead to a seizure-free outcome, although one recent childhood series reported a seizure-free rate of 62% following extratemporal epilepsy surgery. With both temporal and extratemporal resections, additional patients have a reduction in seizures following surgery but are not completely seizure free. The identification of favorable surgical candidates has been the subject of extensive research, and many investigators have examined predictors of outcome following epilepsy surgery. However, the early identification of the potential epilepsy surgery candidate and the optimal timing of surgery have only occasionally been addressed in the literature. This issue is methodologically challenging to study since studies require large numbers of patients with new-onset partial epilepsy who are followed over time. The purpose of this article is to review the current ability for early prediction of medical intractability in patients with surgically remediable epilepsy. Emphasis will be placed on the early prediction of intractable temporal lobe epilepsy in children and adolescents, since temporal lobectomy remains the prototype epilepsy surgery, and early surgery may improve psychosocial outcome in younger patients.     

Electroconvulsive therapy for bipolar depressive and mixed episode with high suicide risk after epilepsy surgery

Mood disturbance is a common comorbid condition of temporal lobe epilepsy before and after surgery. Suicide is more frequent in patients with epilepsy than in the general population. As suicide is a major issue in both epileptic and depressive patients, it is critical to treat aggressively any psychiatric illness with suicidal ideation. We describe two patients who, after temporal lobe surgery, developed a serious bipolar disorder that necessitated electroconvulsive therapy (ECT), despite better seizure control. Unfortunately they were not able to commit to a regular treatment plan with their psychiatrists to prevent a suicide. These patients underwent a course of ECT treatments. After the ECT regimen, acute suicidal intent remitted and was replaced by chronic suicidal ideation without active intent or plan. The patients were then able to commit to a treatment plan regarding their medications and control visits. These cases represent the safe utilization of ECT as a rapid and effective treatment option for bipolar disorder with suicide ideation following epilepsy surgery. Patients and parents should be advised about possible psychiatric disturbances and suicide risk after epilepsy surgery, especially in the presence of a temporal lobe epilepsy, even when seizure control is achieved postoperatively.     

Psychiatric outcome of surgery for temporal lobe epilepsy and presurgical considerations

In recent years, surgery has become a treatment option for some patients with intractable epilepsy, particularly those with temporal lobe epilepsy. Psychiatric disturbances may complicate the postsurgical outcome in some patients and de novo psychiatric symptoms have been reported. In many but not all epilepsy surgical centres, a psychiatric assessment is included as part of the presurgical evaluation of potential candidates for surgery. This review indicates that affective disorders, namely, depression and anxiety, and psychosis are the most frequently reported postsurgical psychiatric disturbances. Whilst there are no absolute psychiatric contraindications to surgery, certain pre-existing psychiatric conditions may need careful consideration as there may be a risk of postsurgical psychiatric complications. Routine pre- and postsurgical psychiatric evaluations in patients undergoing epilepsy surgery are recommended. Clinicians involved in the care of surgical candidates should be aware of the possible psychiatric complications following surgery and ensure that the psychiatric risks are discussed with the patient and family.     

Does antiepileptic drug withdrawal predispose patients undergoing temporal lobe epilepsy surgery to late onset of psychiatric morbidity? A report of three cases

Surgery is an established and increasingly utilized treatment option in medically refractory temporal lobe epilepsy. Many psychiatric problems are known to complicate in the postoperative period. Most studies have a follow-up period of less than 24 months. We report the cases of three patients who developed severe psychiatric problems in the late postoperative period after successful temporal lobectomy for refractory epilepsy — Psychosis, major depression with psychosis, and severe anxiety disorder, respectively. None of the patients had past or family history of psychiatric disease. All three patients had undergone anterior temporal lobectomy on the right side for intractable epilepsy. They remained absolutely seizure-free after surgery. We conclude that psychiatric morbidity may arise de novo long after temporal lobectomy. This association between temporal lobectomy for epilepsy and late onset psychiatric morbidity should be carefully studied. Mechanisms underlying this late complication require deeper understanding of the effects of epilepsy surgery.     

Nociceptive threshold in patients with epilepsy.

Clinical practitioners have often observed in the course of their daily work that the pain thresholds of epileptic patients seem to differ from those of healthy subjects. These patients can suffer from quite severe traumatic lesions without apparently experiencing any pain. Since they are usually under treatment for epilepsy, it is difficult to determine whether the absence of pain is due to these patients' epileptic condition or to its treatment, since most antiepileptic drugs also have analgesic effects. In the present study, it was proposed to assess the pain thresholds of 15 epileptic patients (10 with tonic-clonic seizures generalized at outset and 5 with temporal lobe epilepsy), by measuring the leg flexion nociceptive reflex (or RIII reflex) threshold: the stimulation threshold at which this reflex is triggered is known to be correlated with the pain threshold. The nociceptive threshold of the patients with generalized epilepsy was not found to differ from that of the control population, whereas that of the patients with temporal lobe epilepsy was spontaneously high and was not reversed upon injecting naloxone. These data are discussed from the point of view of the pain pathways and mechanisms possibly involved.     

Temporal Lobe Epilepsy: When Are Invasive Recordings Needed?

Temporal lobe epilepsy (TLE) is the most common type of medically intractable partial epilepsy amenable to surgery. In the majority of cases, the underlying pathology in temporal lobe epilepsy is mesial temporal sclerosis (MTS). Whereas historically invasive recordings were required for most epilepsy surgeries, indications have dramatically changed since the introduction of high-resolution MRI, which uncovers structural lesions in a high percentage of cases. No invasive recordings are required to perform a temporal lobectomy in patients with intractable epilepsy who have structural imaging suggesting unilateral MTS and concordant interictal and ictal surface EEG recordings, functional imaging, and clinical findings. Invasive testing is needed if there is evidence of bitemporal MTS on structural imaging and/or electrophysiologically, and additional information from functional imaging, neuropsychology, and the intracarotid amobarbital (Wada) test also does not help to lateralize the epileptogenic zone. Depth electrodes can be particularly helpful in this setting. However, no surgery is indicated, even without invasive recordings, if bitemporal-independent seizures are recorded by surface EEG and all additional testing is inconclusive. Other etiologies of TLE such as a tumor, vascular malformation, encephalomalacia, or congenital developmental abnormality account for about 30% of all patients who undergo epilepsy surgery. Epilepsy surgery is indicated after limited electrophysiologic investigations if neuroimaging and electrophysiology converge. However, approaches for resection in lesional temporal lobe epilepsy vary among centers. Completeness of resection is crucial and invasive recordings may be needed to guide the resection by mapping eloquent cortex and/or to determine the extent of the non-MRI-visible epileptogenic area. Specific approaches for the different pathologies are discussed because there is evidence that the relationship between the lesions visible on MRI and the epileptogenic zone varies among lesions of different pathologies, and therefore variable surgical strategies must be applied.     

Discontinuation of antiepileptic drugs after pediatric epilepsy surgery

In children with medically intractable seizures, epilepsy surgery is now a widely accepted option. Successful discontinuation of antiepileptic drugs after epilepsy surgery has been reported in adults, but rarely in children. Surgical outcome and need for antiepileptic drugs after temporal and extratemporal lobe resection were retrospectively reviewed for 80 pediatric patients from the Comprehensive Epilepsy Program at the University of Alberta. For 1 year after surgery, children were maintained on at least one antiepileptic drug. Antiepileptic drug discontinuation was attempted in all patients with a nonepileptic electroencephalogram after 1 year seizure-free. Less than half of the patients (44%) eventually relapsed without antiepileptic drugs. Of the 40 patients in the temporal lobe group, 13 (32%) relapsed without antiepileptic drugs, as did 22 of the 40 extratemporal lobe resection patients (55%). Success rates for antiepileptic drug discontinuation after surgery were higher in the temporal lobe than in the extratemporal lobe group. Long-term antiepileptic drugs are not necessary in all cases, and for many children medication can be withdrawn after epilepsy surgery.     

Neuropsychological outcome following focal cortical removal for intractable epilepsy in children

In children, surgery for epilepsy has been recognized as a viable treatment option since publication of S. Davidson and M.A. Falconer's outcome study in 1975 [Lancet North Am Ed 5:1260-3], which demonstrated that medical outcome of children who underwent anterior temporal lobectomy paralleled that of adults. Pediatric surgical programs and the literature on medical outcome have grown considerably since that time, with surgery being offered to children with temporal but also extratemporal epilepsy foci. Comparatively little work has been conducted in the area of neuropsychological outcome. This article outlines differences in adult and pediatric outcome studies, reviews the literature on the intellectual and memory outcome in children, and discusses shortcomings of the pediatric outcome research conducted to date.     

Selection of adult patients for surgical treatment of epilepsy

ABSTRACT— The ideal treatment for epilepsy would produce complete control without toxicity and without side effects.
The physician would like to have surgical therapy as an option for those patients who are not completely free of seizures and for those who are free of seizures but suffer toxic side effects.
Surgery for epilepsy has now become an option that should be considered along with various medical treatment options. The success rates have increased and the complication rates decreased dramatically at those centers performing surgery on a substantial number of cases a year. Patients with complex partial seizures with a clear-cut unilateral temporal lobe focus and highly stereotyped seizures are by far the best candidates for surgery. In the hands of several major epilepsy programs significant improvement in seizure frequency is achieved in greater than 90 per cent of patients.
Patients with sudden drop attacks or uncontrolled generalized tonic-clonic seizures can benefit from section of the corpus callosum. Good results are seen in 85 per cent of the cases.     

The effects of duration of intractable epilepsy on memory function

We assessed whether duration (time since diagnosis) of intractable epilepsy is associated with progressive memory loss in 250 individuals with left or right temporal lobe epilepsy and those diagnosed with psychogenic nonepileptic seizures. Verbal and nonverbal memory function was assessed using several memory assessment measures administered to all individuals as part of a larger neuropsychological assessment. Multivariate multiple regression analyses demonstrated that duration of temporal lobe epilepsy and age of seizure onset are significantly related to verbal memory deficits in patients with epilepsy. The interaction between duration of epilepsy and diagnostic group was nonsignificant, as was the interaction between age at spell onset and diagnostic group. As measured by several neuropsychological memory tests, duration of disease adversely affects verbal memory performance in patients diagnosed with temporal lobe epilepsy. Our study also supports the notion that age at seizure onset significantly affects verbal memory performance in this population. These results have implications for the strategy of treatment and counseling of patients with intractable temporal lobe epilepsy.     

中国汉族人群5-羟色胺转运体基因多态性与非病灶性颞叶癫痫的关联性

目的　初步探讨颞叶癫痫(temporal lobe epilepsy,TLE)的遗传易感因素。方法　采用聚合酶链反应技术,检测263例TLE患者和296名健康对照者的5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT) 基因启动子的基因连锁多态区(gene-linked polymorphic region,LPR) 和第2内含子的可变数目串联重复区(variable number tandem repeat,VNTR) 多态性,分别对所得基因型和等位基因的频率进行相关统计学分析。结果　TLE患者5-HTTLPR多态性的基因型和等位基因频率与正常对照组之间的差异无统计学意义(P>0.05)。TLE患者的5-HTTVNTR的基因型12/12频率高于正常对照组(P<0.01),其等位基因12的频率高于正常对照组(P< 0.01)。携12等位基因者患TLE的相对危险度(OR)是1.435,95%可信区间(CI)为1.096～1.880(P<0.05)。 结论　5-HTTLPR可能不是TLE患者的遗传位点,第2内含子VNTR的等位基因12可能与TLE有一定的关联。     

Epilepsy, surgery, and the elderly

Treatment of elderly patients with epilepsy may present unique challenges to physicians. Co-morbid conditions and drugs to treat such conditions are common in elderly patients, possibly complicating epilepsy therapies that are dependent on drugs alone. For this reason, surgical intervention may be an attractive option for elderly patients with epilepsy, particularly for medically intractable patients with key disease features, such as lateralization and precisely localized epileptic foci. Curative procedures, including lobectomy and lesionectomy, are most likely to lead to seizure freedom, but not all patients are candidates for such procedures. When a curative surgical procedure is not an option, palliative procedures, including vagus nerve stimulation and deep brain stimulation, may be viable options. Vagus nerve stimulation has been reported to reduce seizure rates and improve quality of life in elderly patients with epilepsy. Currently, widespread therapeutic application of deep brain stimulation is limited by risks, costs, and pending studies.     

Current management and surgical outcomes of medically intractable epilepsy

Epilepsy is one of the most common neurologic disorders in the world. While anti-epileptic drugs (AEDs) are the mainstay of treatment in most cases, as many as one-third of patients will have a refractory form of disease indicating the need for a neurosurgical evaluation. Ever since the first half of the twentieth century, surgery has been a major treatment option for epilepsy, but the last 10–15 years in particular has seen several major advances. As shown in relatively recent studies, resection is more effective for medically intractable epilepsy (MIE) than AED treatment alone, which is why most clinicians now endorse a neurosurgical consultation after approximately two failed regimens of AEDs, ultimately leading to decreased healthcare costs and increased quality of life.     

Interictal Temporal Hypoperfusion Is Related to Early-Onset Temporal Lobe Epilepsy

Previous studies of interictal regional cerebral blood flow (rCBF) in temporal lobe epilepsy have shown variable correlations with clinical measures. We used high spatial resolution hexamethyl propyleneamine oxime single photon emission computed tomography (HMPAO SPECT) in 80 consecutive patients with complex partial seizures (CPS), comparing results with those from a large series of normal subjects. Visual image analysis detected abnormalities of rCBF in 41 of 80 (51%; numeric analysis detected abnormalities in 38 of 80). Age at epilepsy onset was significantly younger in patients with temporal hypoperfusion (p = 0.002), and the frequency distribution of hypoperfusion versus age at epilepsy onset was reverse exponential. The results of numerical image analysis showed that degree of hypoperfusion did not vary with age at epilepsy onset. These data suggest a single insult operating early in life as a cause of temporal hypoperfusion, as has been shown for mesial temporal sclerosis (MTS). We could not demonstrate relationships with other clinical variables, including time since last seizure.     

Magnetic resonance imaging and temporal lobe epilepsy

Surgical treatment is a well established option for patients with medically refractory temporal lobe epilepsy. Magnetic resonance imaging (MRI) has revolutionized the evaluation of these patients. New techniques can identify structural, metabolic and functional abnormalities associated with the epileptogenic zone. Mesial temporal sclerosis is the most common pathological finding and presents as hippocampal atrophy, which can be detected by visual inspection in most cases. Volumetric analysis of medial temporal structures offers the advantage of detecting bilateral abnormalities. Magnetic resonance spectroscopy can detect metabolic abnormalities associated with the epileptogenic focus. Functional MRI allows for the non-invasive evaluation of cognitive function, allowing for the localization of the neuroanatomic substrate of motor, sensory and cognitive functions. Intraoperative MRI-based image guided systems are a useful adjunct in the surgical treatment of this epileptic syndrome.     

The effects of cognitive rehabilitation on memory outcome after temporal lobe epilepsy surgery

OBJECTIVE: Epilepsy surgery is a valuable treatment option for patients with pharmacoresistant epilepsy, but seizure freedom is often achieved at the cost of cognitive impairments caused by surgery. The aim of this study was to investigate the short-term effects of cognitive rehabilitation on memory outcome after temporal lobe epilepsy surgery. METHODS: Two groups of patients who underwent temporal lobe resection, one followed (n=55) and one not followed (n=57) by postoperative rehabilitation, were evaluated with respect to memory and attention before and 3 months after temporal lobe surgery. The groups came from different epilepsy centers, but were largely matched with respect to age, sex, type of surgery, and seizure outcome. RESULTS: After surgery, 78% of the patients were seizure-free. Repeated-measures MANOVA revealed a significant "side x surgery" effect on verbal recognition and a "rehabilitation x surgery" effect on verbal learning and recognition. There were no effects for loss in verbal delayed recall or figural memory. Detailed analyses indicated gains as a result of rehabilitation, particularly after right temporal lobe surgery. Attention generally improved. The risk of manifesting losses in verbal memory was about four times higher without than with rehabilitation. CONCLUSIONS: Rehabilitation can counteract the verbal memory decline that is normally seen after temporal lobe resection. Its positive effects were evident particularly with respect to the more cortically associated aspects of verbal learning rather than to the mesial aspects of long-term consolidation/retrieval. Figural memory was not affected at all, and attention improved independent of rehabilitation. Interestingly, left temporal lobe-resected patients, who were most in need of an efficacious rehabilitation, profited less than right temporal lobe-resected patients, indicating that left-sided surgery may reduce the capacity needed for efficient training of verbal memory. Thus, rehabilitation has a positive effect on memory outcome, but its usefulness for risk groups and the question of whether training should be performed after or possibly before surgery are debatable. Further research should also address different interventions, longer-term outcome, and the carryover effects on everyday functioning.     

Epilepsy and Behavior: A Brief History

Behavioral changes-both real and imagined-have formed a halo around epilepsy since antiquity. The myth of epilepsy as a curse has been largely vanquished in modern cultures, but the disorder remains a social stigma for many patients. In ancient Rome people with epilepsy were avoided for fear of contagion, in the Middle Ages they were hunted as witches, and in the first half of our century they were labeled deviants and their marriage and reproduction were restricted by eugenistic medical doctors. Religious conversion experiences can occur in temporal relationship to changes in seizure frequency. Many religious leaders may have had epilepsy. However, changes in religious sentiment are not characteristic of epilepsy patients. Recognized since the late 19th century, postictal psychosis has stimulated theories regarding the mechanism of mania and psychosis. Understanding the pathophysiology of behavioral changes in epilepsy may offer insight into the psychopathology of other diseases.     

Understanding the association of neurocysticercosis and mesial temporal lobe epilepsy and its impact on the surgical treatment of patients with drug-resistant epilepsy

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is one of the most common types of focal epilepsies. This is an epileptic syndrome commonly associated with treatment-resistant seizures, being also the most prevalent form of drug-resistant epilepsy which is treated surgically in most epilepsy surgery centers. Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system, and one of the most common etiological agents of focal epilepsy, affecting millions of patients worldwide. Recently, researchers reported a curious association between MTLE-HS with NCC, but this association remains poorly understood. Some argue that calcified NCC lesions in MTLE-HS patients is only a coincidental finding, since both disorders are prevalent worldwide. However, others suppose there might exist a pathogenic relationship between both disorders and some even suspect that NCC, by acting as an initial precipitating injury (IPI), might cause hippocampal damage and, eventually, MTLE-HS. In this review, we discuss the various reports that examine this association, and suggest possible explanations for why calcified NCC lesions are also observed in patients with MTLE-HS. We also propose mechanisms by which NCC could lead to MTLE-HS. Finally, we discuss the implications of NCC for the treatment of pharmacologically-resistant focal epilepsies in patients with calcified NCC or in patients with MTLE-HS and calcified NCC lesions. We believe that investigations in the relationship between NCC and MTLE-HS might offer further insights into how NCC may trigger epilepsy, and into how MTLE-HS originates. Moreover, observations in patients with drug-resistant epilepsy with both NCC and hippocampal sclerosis may not only aid in the understanding and treatment of patients with MTLE-HS, but also of patients with other forms of dual pathologies aside from NCC.This article is part of a Special Issue titled Neurocysticercosis and Epilepsy.     

Ego functions in epilepsy

Two groups of epilepsy patients (28 patients with temporal lobe epilepsy and 15 patients with primary generalized epilepsy) entered a study of personality traits related to epilepsy, based on a modification of Bellak's semistructured interview for assessment of ego strength. Two groups of subjects served as controls: 15 patients with a non-neurological but relapsing disorder, psoriasis, and 15 healthy volunteers. Compared with the group of healthy volunteers, a decreased adaptive level of ego functioning was found in the epilepsy groups, regardless of seizure types and EEG findings, and, to a lesser extent, compared with the psoriasis group. Areas of ego functioning most affected were "reality testing", "cognitive functioning", "integrative functioning" and "regulation and control of drives". Patients with more than one type of seizure were the most affected, as were patients who were younger than 15 years when the disease began. The number of anticonvulsants administered did not influence the results. No difference on adaptive level of ego functioning was found between the group with primary generalized epilepsy and the group with temporal lobe epilepsy. Similarly, the temporal lobe epilepsy group with predominantly right-sided and left-sided EEG changes, respectively, showed similar adaptive levels of ego functioning.