Recent developments in the epidemiology of epilepsy

Epidemiological incidence data are important to determine those who are at risk of epilepsy and to understand the aetiology of the condition. A number of studies have been reported recently, which allow comparisons across populations. There appears to be geographical variation in the incidence of epilepsy, with a higher incidence in rural South America than in developed countries: no large scale incidence studies have yet been carried out in Africa or Asia. A consistent pattern suggesting that the onset of epilepsy occurs at the extremes of life has also been shown. Although a number of factors are often identified as causes of epilepsy, studies have identified a definitive aetiology in only one-third of all newly diagnosed cases. Epidemiological studies have, however, confirmed the importance of postnatal insults and quantified the risk. Family history may also be considered a risk factor for epilepsy in epidemiological terms.     

MEG abnormalities and mechanisms of surgical failure in neocortical epilepsy

Objective

Epilepsy surgery fails to achieve seizure freedom in 30%–40% of cases. It is not fully understood why some surgeries are unsuccessful. By comparing interictal magnetoencephalography (MEG) band power from patient data to normative maps, which describe healthy spatial and population variability, we identify patient-specific abnormalities relating to surgical failure. We propose three mechanisms contributing to poor surgical outcome: (1) not resecting the epileptogenic abnormalities (mislocalization), (2) failing to remove all epileptogenic abnormalities (partial resection), and (3) insufficiently impacting the overall cortical abnormality. Herein we develop markers of these mechanisms, validating them against patient outcomes.

Methods

Resting-state MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band-power spatial maps were computed using source-localized recordings. Patient and region-specific band-power abnormalities were estimated as the maximum absolute z-score across five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative magnetic resonance imaging (MRI). We hypothesized that our mechanistically interpretable markers would discriminate patients with and without postoperative seizure freedom.

Results

Our markers discriminated surgical outcome groups (abnormalities not targeted: area under the curve [AUC] = 0.80, p = .003; partial resection of epileptogenic zone: AUC = 0.68, p = .053; and insufficient cortical abnormality impact: AUC = 0.64, p = .096). Furthermore, 95% of those patients who were not seizure-free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure-free.

Significance

The mapping of abnormalities across the brain is important for a wide range of neurological conditions. Here we have demonstrated that interictal MEG band-power mapping has merit for the localization of pathology and improving our mechanistic understanding of epilepsy. Our markers for mechanisms of surgical failure could be used in the future to construct predictive models of surgical outcome, aiding clinical teams during patient pre-surgical evaluations.     

The role of neuroimaging in the surgical treatment of epilepsy

ABSTRACT— Resective surgical treatment of medically intractable epilepsy requires accurate identification of the site and extent of the epileptogenic zone responsible for habitual seizures. Epileptogenicity per se is demonstrated electrophysiologically, but interictal and ictal EEG transients, whether recorded extracranially or intracranially, propagate widely and can give rise to false lateralizing and false localizing information. Neuroimaging techniques provide additional important information which greatly enhances confidence in localization derived electrophysiologically. Structural imaging with X-ray computed tomography and magnetic resonance imaging, as well as functional imaging with positron emission tomography, single photon emission computed tomography, and computerized mapping of electromagnetic activity, used together with other tests of focal functional deficit, 1) increase the confidence with which surgical resection can be performed on the basis of noninvasive tests alone, 2) aid in developing appropriate strategy for intracranial electrode recording when this is necessary, and 3) supplement results of invasive studies sufficiently to justify surgical resection in some patients who otherwise might be rejected for surgery. Addition of these new techniques, therefore, has increased the number of patients considered candidates for surgery, decreased the number of invasive procedures necessary before surgery can be performed, and increased the accuracy of surgical resection.     

颞叶新皮质癫痫手术的疗效分析

目的分析总结颞叶新皮质癫痫患者临床特征、术前评估、手术方法和疗效。方法对36例颞叶新皮质癫痫行神经电生理、MRI,正电子发射计算断层显像计算机体层扫描（PET—CT）定位,术中皮层电极和深部电极描记,联合采用不同术式以及术后随访6个月至2年的疗效观察。结果疗效按谭启富的标准分类：Ⅰ级12例,Ⅱ级11例,Ⅲ级8例,Ⅳ级5例,Ⅴ级0例。病理报告：胶质增生23例;微小血管畸形5例;灰质异位1例,无异常发现7例。无手术致残和死亡。结论联合采取不同术式,如：行海马及杏仁核部分切除,对颞叶新皮质癫痫可达到良好的治疗效果,且无严重手术并发症。     

Relationship between preoperative hypometabolism and surgical outcome in neocortical epilepsy surgery

Purpose: Fluorine‐18‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) hypometabolism has been used to localize the epileptogenic zone. However, glucose hypometabolism remote to the ictal focus is common and its relationship to surgical outcome has not been considered in many studies. We investigated the relationship between surgical outcome and FDG‐PET hypometabolism topography in a large cohort of patients with neocortical epilepsy. Methods: We identified all patients (n = 68) who had interictal FDG‐PET between 1994 and 2004 and who underwent resective epilepsy surgery with follow up for more than 2 years. The volumes of significant FDG‐PET hypometabolism involving the resected epileptic focus and its surrounding regions (perifocal hypometabolism) and those distant to and not contiguous with the perifocal hypometabolism (remote hypometabolism) were determined statistically using Statistical Parametric Mapping (voxel threshold p = 0.01, extent threshold ≥250 voxels, uncorrected cluster‐level significance p < 0.05) and were compared with magnetic resonance imaging (MRI) and clinical and demographic variables using a multiple logistic regression model to identify independent predictors of seizure outcome. Key Findings: Remote hypometabolism was present in 39 patients. Seizure freedom was 49% (19 of 39 patients) in patients with glucose hypometabolism remote from the epileptogenic zone compared to 90% (26 of 29 patients) in patients without remote hypometabolism. In 43 patients with an MRI‐identified lesion, seizure freedom was 79% (34 of 43 patients). In patients with normal MRI, cortical dysplasia was the predominant pathologic substrate. Multiple logistic regression analysis identified a larger volume of significant remote hypometabolism (p < 0.005) and absence of a MRI‐localized lesion (p = 0.006) as independent predictors of continued seizures after surgery. Significance: In patients with widespread glucose hypometabolism that is statistically significant when compared to controls, epilepsy surgery may not result in complete seizure freedom despite complete removal of the MRI‐identified lesion. The volume of significant glucose hypometabolism remote to the ictal‐onset zone may be an independent predictor of the success of epilepsy surgery.     

综合应用定位技术和外科方法治疗顽固性癫痫

目的：研究顽固性癫痫的致痫灶精确定位和外科治疗方法。方法：对185例顽固性癫痫患综合应用三维痫灶精确定位诊疗计划系统及影像学检查进行术前、术中致痫灶三维精确定位，采用癫痫外科综合治疗方案（手术治疗、介入放射治疗、定向放射治疗等）毁损致痫灶、阻断致痫网，以治疗顽固性癫痫。结果：术中64导皮层电极及8导深部电极检测证实该定位系统定位准确可靠。必要的影像学检查有助于痫灶定性定位诊断及治疗方案设计。随访疗效评估显效率达到87．0％，总有效率达到94．6％，术后神经功能保持良好，无明显后遗症。结论：综合应用三维痫灶精确定位诊疗计划系统和影像学检查对痫灶进行定位以及采取癫痫外科综合治疗方式是治疗顽固性癫痫的较好方法。     

Ictal electrocorticographic findings related with surgical outcomes in nonlesional neocortical epilepsy

PURPOSE: To characterize ictal electrocorticographic features related to surgical outcomes in nonlesional neocortical epilepsy (NE). METHODS: We analyzed 187 ictal electrocorticograms (ECoG) obtained from 18 patients who had undergone presurgical evaluation and subsequent neocortical resections (frontal: seven, parietal: one, occipital: four, multilobar: six). None of them had any MRI-detectable lesions. Various ECoG data sets recorded from eight patients who achieved a favorable surgical outcome (either seizure free or more than 90% reduction of seizure frequencies) were compared with that from ten patients with unfavorable outcome (less than 90% reduction of seizure frequencies) (follow up duration: 47+/-11 months). RESULTS: Reproducible ictal onset zone (IOZ) in recurrent seizures (P=0.013) and persistent ictal discharges in IOZ from the onset to the end of seizure (P=0.004) were found more frequently in the patients with good outcome. Ictal onset patterns consisting of low voltage fast or high amplitude beta spikes predicted a good surgical outcome while rhythmic sinusoidal activity or rhythmic spike/sharp waves of slow frequency were predictive of poor outcome (P=0.01). The ictal onset rhythm consisting of gamma or beta frequencies was more prevalent in the favorable group (P=0.015). CONCLUSIONS: The presence of stable ictal circuit suggested by the consistent earliest activation of specific electrodes in the repetitive seizures (reproducible IOZ) and the active participation of IOZ throughout the attack were valuable prognostic factors in addition to the morphology and frequency of ictal onset rhythm.     

脑磁图对病灶性新皮质癫(疒间)术前评估的价值

目的 研究病灶性新皮质癫(疒间)发作间期MEG 和MRI 一致性与预后的关系.方法 23 例病灶性新皮质癫(疒间)接受了术前评估及手术治疗,所有患者术前均接受MEG 检测,数据分析处理采用等价电流偶极子(ECD)法和合成孔径法(SAMg2).7 例患者接受了颅内电极植入后长程视频皮层脑电图监测.术后随访一年以上并运用Engel 法评价预后.结果 MEG 与MRI 一致的病例手术有效率(Engel class I or II)及术后无发作率(Engel class IA)均优于不一致者.结论 病灶性新皮质癫(疒间),MEG 结果与MRI 结果一致时手术效果良好,对此类病例不需要再进行颅内电极植入行癫(疒间)灶定位,颅内电极植入仅适用于MEG 结果与MRI 结果不一致的病例或需要功能区定位者.     

Recent developments in cognitive fMRI for temporal lobe epilepsy

Epilepsy is frequently accompanied by severe cognitive side effects. Temporal lobe epilepsy (TLE), and even successful surgical treatment, may affect cognitive function, in particular language as well as verbal and visual memory function. Epilepsy arising from the temporal lobe can be controlled surgically in up to 70% of patients. The goals of epilepsy surgery are to remove the brain areas generating the seizures without causing or aggravating neuropsychological deficits. This requires accurate localization of the brain areas generating the seizures (“epileptogenic zone”) and the areas responsible for motor and cognitive functions, such as language and memory (“essential brain regions”) during presurgical evaluation. In the past decades, functional magnetic resonance imaging (fMRI) has been increasingly used to noninvasively lateralize and localize not only primary motor and somatosensory areas, but also brain areas that are involved in everyday language and memory processes. The imaging modality also shows potential for predicting the effects of temporal lobe resection on language and memory function. Together with other MRI modalities, cognitive fMRI is a promising tool to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared.

The aim of this review is to provide an overview of recent developments and practical recommendations for the clinical use of cognitive fMRI in TLE.

     

Interictal magnetoencephalographic findings related with surgical outcomes in lesional and nonlesional neocortical epilepsy

Purpose

To investigate whether interictal magnetoencephalography (MEG) concordant with other techniques can predict surgical outcome in patients with lesional and nonlesional refractory neocortical epilepsy (NE).

Methods

23 Patients with lesional NE and 20 patients with nonlesional NE were studied. MEG was recorded for all patients with a 275 channel whole-head system. Synthetic aperture magnetometry (SAM) with excess kurtosis (g2) and conventional Equivalent Current Dipole (ECD) were used for MEG data analysis. 27 Patients underwent long-term extraoperative intracranial video electroencephalography (iVEEG) monitoring. Surgical outcomes were assessed based on more than 1-year of post-surgical follow-up using Engel classification system.

Results

As we expected, both favorable outcomes (Engel class I or II) and seizure freedom outcomes (Engel class IA) were higher for the concordance condition (MEG findings are concordant with MRI or iVEEG findings) versus the discordance condition. Also the seizure free rate was significantly higher (χ² = 5.24, P < 0.05) for the patients with lesional NE than for the patients with nonlesional NE. In 30% of the patients with nonlesional NE, the MEG findings proved to be valuable for intracranial electrode implantation.

Conclusions

This study demonstrates that a favorable post-surgical outcome can be obtained in most patients with concordant MEG and MRI results even without extraoperative iVEEG monitoring, which indicates that the concordance among different modalities could indicate a likelihood of better postsurgical outcomes. However, extraoperative iVEEG monitoring remains prerequisite to the patients with discordant MEG and MRI findings. For nonlesional cases, our results showed that MEG could provide critical information in the placement of intracranial electrodes.     

Extent of neocortical resection and surgical outcome of epilepsy: Intracranial EEG analysis

Purpose: Intracranial electroencephalography (EEG) monitoring is an important process in the presurgical evaluation for epilepsy surgery. The objective of this study was to identify the ideal resection margin in neocortical epilepsy guided by subdural electrodes. For this purpose, we investigated the relationship between the extent of resection guided by subdural electrodes and the outcome of epilepsy surgery. Methods: Intracranial EEG studies were analyzed in 177 consecutive patients who had undergone resective epilepsy surgery. We reviewed various intracranial EEG findings and resection extent. We analyzed the relationships between the surgical outcomes and intracranial EEG factors: the frequency, morphology, and distribution of ictal‐onset discharges, the propagation speed, and the time lag between clinical and intracranial ictal onset. We also investigated whether the extent of resection, including the area showing ictal rhythm and various interictal abnormalities—such as frequent interictal spikes, pathologic delta waves, and paroxysmal fast activity—influenced the surgical outcome. Results: Seventy‐five patients (42%) were seizure free. A seizure‐free outcome was significantly associated with a resection that included the area showing ictal spreading rhythm during the first 3 s or included all the electrodes showing pathologic delta waves or frequent interictal spikes. However, subgroup analysis revealed that the extent of resection did not affect the surgical outcome in lateral temporal lobe epilepsy. Conclusions: The extent of resection is closely associated with surgical outcome, especially in extratemporal lobe epilepsy. Resection that includes the area with total pathologic delta waves and frequent interictal spikes predicts a good surgical outcome.     

Awake craniotomy: controversies, indications and techniques in the surgical treatment of temporal lobe epilepsy

In 1886, Victor Horsley excised an epileptogenic posttraumatic cortical scar in a 23-year-old man under general anaesthesia and discussed his choice of anaesthesia: "I have not employed ether in operations on man, fearing that it would tend to cause cerebral excitement; chloroform, of course, producing on the contrary, well-marked depression." His concerns regarding anaesthesia are reiterated 100 years later as evidenced by the ongoing controversy over the choice of anaesthetic in surgical procedures for epilepsy. The current controversies regarding the necessity for local anaesthesia in temporal lobe epilepsy operations concern the utility of electrocorticography in surgical decision making, its relationship to seizure outcome and the value of intraoperative language mapping in dominant temporal lobe resections. The increasing sophistication of pre-operative investigation and localization of both areas of epileptogenesis and normal brain function and the introduction of minimally invasive surgical techniques and smaller focal resections are changing the indications for local anaesthesia in temporal lobe epilepsy. Thus, indications which were previously absolute are now perhaps relative. This article reviews the current indications for craniotomy under local anaesthesia in the surgical treatment of temporal lobe epilepsy.     

Pre-surgical evaluation and surgical outcome of 41 patients with non-lesional neocortical epilepsy.

Pre-surgical evaluation and the surgical treatment of non-lesional neocortical epilepsy is one of the most challenging areas in epilepsy surgery. The aim of this study was to evaluate the surgical outcome and the diagnostic role of ictal scalp electroencephalography (EEG), interictal (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and ictal technetium-99m hexamethylpropyleneamine oxime single photon emission tomography ( (99m)Tc-HMPAO SPECT). In 41 non-lesional neocortical epilepsy patients (16 frontal lobe epilepsy, 11 neocortical temporal lobe epilepsy, seven occipital lobe epilepsy, four parietal lobe epilepsy, and three with multifocal onset) who underwent surgical treatment between December 1994 and July 1998, we evaluated the surgical outcome with a follow-up of at least 1 year. The localizing and lateralizing values of ictal scalp EEG, interictal FDG-PET, and ictal SPECT were evaluated in those patients with good surgical outcome. Ictal scalp EEG had the highest diagnostic sensitivity in the localization of epileptogenic foci (69.7% vs. 42.9% for FDG-PET and 33.3% for ictal SPECT; P= 0.027). However, no significant difference was found in the lateralization of the epileptogenic hemisphere among the three modalities (78.8% for ictal scalp EEG, 57.2% for FDG-PET, and 55.5% for ictal SPECT; P= 0.102). During a mean follow-up of 2.77 +/- 1.12 years, 33 (80.5%) showed good surgical outcome (seizure free or seizure reduction >90%), including 16 (39.0%) seizure free patients. Ictal scalp EEG was the most useful diagnostic tool in the localization of epileptogenic foci. Interictal FDG-PET and ictal SPECT were found to be useful as complementary and, sometimes, independent modalities. Many patients with non-lesional neocortical epilepsy would benefit from surgical treatment.     

Emerging surgical and radiotherapeutic techniques for treating epilepsy

PURPOSE OF REVIEW: Recent advances in epilepsy surgery have developed a resurgence of interest in the use of surgical techniques for the treatment of intractable epilepsy. RECENT FINDINGS: More invasive procedures such as hemispherectomy and multiple subpial transection have become more popular. Disconnective techniques such as multiple subpial transection have provided a surgical option for patients whose epileptogenic zone resides in the eloquent cortex. Alternatively, new minimally invasive neurostimulation therapies have been introduced to preserve maximal cerebral tissue. Radiosurgery has been recently utilized in the treatment of epilepsy with preliminary promising results. SUMMARY: In this analysis, the authors will attempt to review the more recent surgical approaches and their indications for the treatment of medically intractable epilepsy. For patients with the epileptogenic zone in the noneloquent cortex, seizure focus resection remains the most reasonable approach to therapy.     

Recent advances in the diagnosis and treatment of epilepsy

Recent advances in the diagnosis and treatment of epilepsies are discussed with special consideration of epidemiology and classification, progress in neuroimaging, electrophysiological studies using EEG and MEG, initiation of medical and surgical treatment, the role of new antiepileptic drugs and selected aspects of genetics of idiopathic epilepsies. In addition from conclusions obtained by the review of recent developments suggestions for future work in Europe are discussed. A constructive approach from multicenter studies requires homologous definitions, documentations and standardization of procedures of trials for European multicenter studies.     

Recent developments in the diagnosis and treatment of sleep disorders

The publication of a new nosology of sleep and arousal disorders in 1979 established the need for differential diagnosis of sleep disorders based on polysomnographic evaluations as well as medical history and physical examination. This review of recent developments in diagnosing and treating sleep disorders covers such topics as prevalence, findings related to sleeping pills and insomnia, effects of depression on sleep, and managing the elderly patient with disturbed sleep. The authors caution against misuse of hypnotic drug therapy for treatment of insomnia and encourage physicians to inquire about sleep patterns even when a patient is presenting a seemingly unrelated problem.     

Recent developments in the diagnosis and treatment of status epilepticus

Despite increased understanding of its potential complications, status epilepticus (SE) frequently remains difficult to diagnose and treat. Advances in continuous electroencephalogram (EEG) monitoring facilitate more rapid identification of SE, even without visible clinical signs of seizures. EEG monitoring assists in modifying SE treatment and in making a prognosis. Despite the improved recognition of SE, some patients continue to seize after treatment with intravenous benzodiazepines and other medications. There are new uses for valproic acid, levetiracetam, and topiramate, and they have evidence of efficacy in treating different forms of SE. If medical treatments do not terminate SE, other interventions, such as surgery and stimulation procedures, may promote seizure cessation. This article reviews recent studies evaluating the use of continuous EEG monitoring in the setting of SE, new uses of anticonvulsants, and nonpharmacologic interventions for SE.     

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy

Aims

Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using ¹⁸F-FDG-PET.

Methods

A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). ¹⁸F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient.

Results

The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05).

Conclusions

The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.