Intraoperative ultrasound to define focal cortical dysplasia in epilepsy surgery

Focal cortical dyplasia (FCD) is a frequent cause of medication-resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize.     

A population-based study of long-term outcomes of cryptogenic focal epilepsy in childhood: cryptogenic epilepsy is probably not symptomatic epilepsy

Purpose: To compare long‐term outcome in a population‐based group of children with cryptogenic versus symptomatic focal epilepsy diagnosed from 1980 to 2004 and to define the course of epilepsy in the cryptogenic group. Methods: We identified all children residing in Olmsted County, MN, 1 month through 17 years, with newly diagnosed, nonidiopathic focal epilepsy from 1980 to 2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long‐term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings: Of 359 children with newly diagnosed epilepsy, 215 (60%) had nonidiopathic focal epilepsy. Of these, 206 (96%) were followed for >12 months. Ninety‐five children (46%) were classified as symptomatic. Median follow‐up from diagnosis was similar in both groups, being 157 months (25%, 75%: 89, 233) in the cryptogenic group versus 134 months (25%, 75%: 78, 220) in the symptomatic group (p = 0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long‐term outcome was significantly better in those with cryptogenic versus symptomatic etiology (intractable epilepsy at last follow‐up, 7% vs. 40%, p < 0.001; seizure freedom at last follow‐up, 81% vs. 55%, p < 0.001). Of those who achieved seizure freedom at final follow‐up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p = 0.01). One‐third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure‐free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly predict outcome in the cryptogenic group. Significance: More than half of childhood nonidiopathic localization‐related epilepsy is cryptogenic. This group has a significantly better long‐term outcome than those with a symptomatic etiology, and should be distinguished from it.     

BOLD signal changes preceding negative responses in EEG‐fMRI in patients with focal epilepsy

Purpose: In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level–dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus. Methods: Eighty‐two patients with focal epilepsy who underwent EEG‐fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from ?9 to +9 s around the spike. Results: Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of ?5 to ?9 s. Discussion: This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs.     

Minimally resective epilepsy surgery in MRI‐negative children

Aim. Performing epilepsy surgery on children with non‐lesional brain MRI often results in large lobar or multilobar resections. The aim of this study was to determine if smaller resections result in a comparable rate of seizure freedom. Methods. We reviewed 25 children who had undergone focal corticectomies restricted to one aspect of a single lobe or the insula at our institution within a 5.5‐year period. Data collected in the comprehensive non‐invasive pre‐surgical evaluation (including scalp video‐EEG, volumetric MRI, functional MRI, EEG source localization, and SPECT and PET), as well as from invasive recordings performed in each patient, was reviewed. Data from each functional modality was identified as convergent or divergent with the epileptogenic zone using image coregistration. Specific biomarkers (from extra‐operative and invasive testing) previously indicated to be indicative of focal epileptogenicity were used to further tailor each resection to an epileptogenic epicentre. Tissue pathology and postoperative outcomes were obtained from all 25 patients. Results. Two years postoperatively, 15/25 (60%) children were seizure‐free, three (12%) experienced >90% reduction in seizure frequency, two (8%) had a 50–90% reduction in seizure frequency, and the remaining five (20%) had no change in seizure burden. There was no significant difference in outcome based on numerous pre‐ and postoperative factors including location of resection, the number of preoperative functional tests providing convergent data, and tissue pathology. Conclusion. In MRI‐negative children with focal epilepsy, an epileptogenic epicentre within a larger epileptogenic zone can be identified when specific biomarkers are recognized on non‐invasive and invasive testing. When such children undergo resection of a small, well‐defined epileptogenic epicentre, favourable outcomes can be achieved.     

Taylor’s focal cortical dysplasia increases the risk of sleep‐related epilepsy

Purpose: To analyze the topography of the epileptogenic zone (EZ) and the etiologic substrate as risk factors for sleep‐related focal epilepsy. Methods: Three hundred three patients (172 males and 131 females, mean age at surgery 25.6 ± 13.1 years), who were seizure‐free after resective surgery for drug‐resistant focal epilepsy, were retrospectively reviewed. Statistical analysis was conducted to evaluate the risk of presenting sleep‐related epilepsy (SRE) against topography of resection (assumed to correspond or to include the EZ) and results of histology. Results: Thirty‐nine patients (12.8%) presented with an SRE. At bivariate analysis, a higher frequency of SRE was associated with a frontal lobe EZ (p = 1.94 × 10^?9) and Taylor’s FCD (TFCD, p = 2.20 × 10^?16), whereas architectural FCD (p = 0.00977), ganglioglioma (p = 0.02508), and mesial temporal sclerosis (p = 2.47 × 10^?5) were correlated with a reduced frequency of SRE. Multivariate analysis demonstrated that the only variable significantly associated with SRE was the presence of a TFCD, which increased 14‐fold the risk of SRE [p = 1.66 × 10^?10; risk ratio (RR) = 14.44]. Discussion: In this study, we have demonstrated a significant and strong association between SRE and TFCD in a select population of patients with drug‐resistant focal epilepsy submitted to surgical resection of the EZ. Although our results cannot be applied to the entire spectrum of SRE, the presence of TFCD as the underlying etiology should be considered when evaluating patients with SRE, because surgery can provide excellent results on seizures in these cases.     

Transient and chronic seizure‐induced inflammation in human focal epilepsy

In animal models, inflammation is both a cause and consequence of seizures. Less is known about the role of inflammation in human epilepsy. We performed positron emission tomography (PET) using a radiotracer sensitive to brain inflammation in a patient with frontal epilepsy ~36 h after a seizure as well as during a seizure‐free period. When statistically compared to a group of 12 matched controls, both of the patient's scans identified a frontal (supplementary motor area) region of increased inflammation corresponding to his clinically defined seizure focus, but the postseizure scan showed significantly greater inflammation intensity and spatial extent. These results provide new information about transient and chronic neuroinflammation in human epilepsy and may be relevant to understanding the process of epileptogenesis and guiding therapy.     

聚焦超声治疗猫功能区局灶性癫痫的可行性研究

目的探讨聚焦超声波治疗猫功能区局灶性癫痫的可行性及有效性。方法建立青霉素诱发的猫运动区局灶性癫痫模型。根据换能器功率及治疗时间不同,分为2W/3s组,2W/5s组,3W/3s组及3W/5s组,通过行为学观察及脑电图(EEG)监测,比较各组在控制癫痫发作方面的效果;通过对治疗区脑组织进行组织病理学观察,探讨聚焦超声波治疗功能区局灶性癫痫的机制。结果在控制癫痫发作方面,2W/5s组及3W/3s组治疗效果与2W/3s组及3W/5s组相比,差异具有统计学意义(P<0.05)。其病理学改变均表现为皮质浅层神经细胞的缺血性改变甚至凝固性坏死,皮层损伤深度随着换能器功率和持续时间的改变而变化。结论适当功率及作用时间的聚焦超声波能有效地破坏和切断皮层的水平纤维联系,同时该皮质的正常功能仍可以保留。因此,聚焦超声波治疗功能区局灶性癫痫的方法安全可行。     

Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia

Objective

The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).

Sleep related epilepsy in focal cortical dysplasia type 2: Insights from sleep recordings in presurgical evaluation

ObjectiveTo determine the relationship between seizure onset, sleep stage and focal cortical dysplasia type 2 (FCD2) location in sleep related epilepsy (SRE).MethodsWe reviewed scalp video-EEG data of 77 patients with SRE among 130 surgically treated patients with histologically confirmed FCD2. Seizure onset was classified as occurring during NREM, REM and after arousal.ResultsSleep recordings were available for 65 patients (37 males, 7–49 years old). FCD2 was located in frontal lobe in 46 (71%) and in extra-frontal regions in 19, including the temporal lobe in 6. MRI was negative/doubtful in 35 cases. Interictal rhythmic/pseudorhythmic spike rate increased from 31% during waking to 65% during sleep. Seizure onset occurred from NREM in 46 cases (71%), mostly from stage 2, and after arousal in 14 (22%). Seizures occurring from NREM/REM sleep were significantly more frequent in frontal (89%) compared to extra-frontal location (42%), whilst arousal preceded seizure onset more often in extra-frontal (58%) compared to frontal location (7%).ConclusionsNREM seizure onset is the most common ictal pattern in SRE due to frontal FCD2 whereas preceding arousal points to extra-frontal regions.SignificanceSleep recordings may help for FCD2 localisation and suggest topography dependent impact on sleep related epileptic networks.     

Expression and localization of voltage dependent potassium channel Kv4.2 in epilepsy associated focal lesions

An increasing number of observations suggest an important role for voltage-gated potassium (Kv) channels in epilepsy. We studied the cell-specific distribution of Kv4.2, phosphorylated (p) Kv4.2 and the Kv4.2 interacting protein NCS-1 using immunocytochemistry in different epilepsy-associated focal lesions. In hippocampal sclerosis (HS), Kv4.2 and pKv4.2 immunoreactivity (IR) was reduced in the neuropil in regions with prominent neuronal cell loss. In both HS and malformations of cortical development (MCD), intense labeling was found in neuronal somata, but not in dendrites. Strong NCS-1 IR was observed in neurons in all lesion types. Western blot analysis demonstrated an increase of total Kv4.2 in all lesions and activation of the ERK pathway in HS and ganglioglioma. These findings indicate that Kv4.2 is expressed in both neuronal and glial cells and its regulation may involve potassium channel interacting proteins, alterations in the subcellular localization of the channel, as well as phosphorylation-mediated posttranslational modifications.