Functional MRI interactions between dysplastic nodules and overlying cortex in periventricular nodular heterotopia

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development associated with epilepsy. It is unclear whether the epileptogenic focus is the nodule, overlying cortex, or both. We performed electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in a patient with bilateral PVNH, capturing 45 "left temporal" epileptiform discharges. The relative time at which fMRI-involved regions became active was assessed. Additionally, nodule-cortex interactions were explored using fMRI functional connectivity. There was EEG-fMRI activity in specific periventricular nodules and overlying cortex in the left temporoparietal region. In both nodules and cortex, the peak BOLD response to epileptiform events occurred earlier than expected from standard fMRI hemodynamic modeling. Functional connectivity showed nodule-cortex interactions to be strong in this region, even when the influence of fMRI activity fluctuations due to spiking was removed. Nonepileptogenic, contralateral nodules did not show connectivity with overlying cortex. EEG-fMRI and functional connectivity can help identify which of the multiple abnormal regions are epileptogenic in PVNH.     

Steroid sulfatase deficiency with bilateral periventricular nodular heterotopia

This report presents a case of steroid sulfatase deficiency with bilateral periventricular nodular heterotopia. A 13-year-old male was diagnosed as having steroid sulfatase deficiency because steroid sulfatase activity was not detected in his leukocytes. In deoxyribonucleic acid studies, steroid sulfatase locus and adjacent loci were found to be deleted in his deoxyribonucleic acid. Cranial magnetic resonance imaging revealed periventricular nodular heterotopia, disclosing an irregular contour of the lateral walls of the lateral ventricles due to small nodular masses that were isointense as to the gray matter. In steroid sulfatase deficiency patients, bilateral periventricular nodular heterotopia must be considered.     

Outcome of bilateral periventricular nodular heterotopia in monozygotic twins with megalencephaly

Bilateral periventricular nodular heterotopia (BPNH) is a neuronal migration disorder, characterized by grey-matter cellular rests in the periventricular regions. Patients frequently present with seizures during childhood or later in life. Monozygotic twin sisters were found to have enlarged head circumferences (>95th centile) during a routine medical visit at 6 months of age. A brain CT scan revealed grey-matter cellular rests in the subependymal regions extending to the subcortical white matter. In some areas these cell aggregates had nodular margins, consistent with the diagnosis of BPNH. At 6 years of age they are cognitively and neurologically normal. They have not had any seizures and their heads continue to grow along the 95th centile.     

Neural networks underlying epileptic humming

PURPOSE: Humming is a rare automatism occurring in partial seizures that has received little attention. Its study could shed light on the neural networks underlying melodic expression. In this study, we examined the anatomoelectroclinical correlates of humming during epileptic seizures METHODS: Three patients undergoing presurgical stereoelectroencephalography (SEEG) for medically intractable temporal lobe epilepsy were studied. Coherence analysis of SEEG activity was carried out to study the functional coupling of different regions of the brain, whereas time-frequency (TF) analysis was conducted to assess epileptic discharge patterns. Changes in coherence were studied to identify the neural structures/systems implicated in humming. RESULTS: Humming began after the onset of seizures generated in medial limbic regions of the temporal lobe. At seizure onset, coherence analysis showed an increase in amygdala-hippocampus coupling. Humming began after the onset of a rhythmic discharge over lateral regions of the superior temporal gyrus (STG). A highly significant increase in coherence was observed between prefrontal regions and the STG. TF analysis of the STG discharge showed a reproducible pattern with a single fundamental frequency and associated harmonics. This frequency was approximately 6 Hz for two patients and 15 Hz for one patient. CONCLUSIONS: These findings suggest that the occurrence of humming during epileptic seizures of the temporal lobe is associated with activity in a neural network involving the STG and the inferior frontal gyrus.     

Procaine-induced seizures in epileptic monkeys with bilateral hippocampal foci.

Intravenous procaine HCl given at low doses (0.5-2.5 mg/kg) to two monkeys with bilateral alumina hippocampal foci depressed interictal spiking or had little effect. At 5.0 mg/kg unilateral limbic activation occurred. At 10.0 mg/kg unilateral or bilateral limbic activation and generalized seizures could be evoked within 3-10 min. At higher doses (15 and 20 mg/kg) bilateral limbic activation or brief (one min) generalized seizures occurred. The unilateral-onset psychomotor seizures were not identical to spontaneous psychomotor seizures, and the generalized seizures never occurred spontaneously in these monkeys. However, these results do indicate that procaine challenges may selectively activate limbic epileptogenic areas without activation of debilitating generalized tonic-clonic seizures.     

Unilateral periventricular nodular heterotopia associated with diffuse areas of cerebral functional abnormalities

A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic resonance imaging revealed a unilateral periventricular nodular heterotopia near the occipital ventricular right horn. Interictal and ictal electroencephalographic recordings showed bilateral specific epileptiform anomalies in the occipital region and asynchronous slow waves in frontal areas. Single photon emission computed tomography documented a reduction in regional cerebral blood flow in an area of the left occipital cortex and a symmetric increase in tracer uptake in the frontal lobes. The neuropsychologic assessment revealed a dysfunction of the frontal associative areas. Data collected led the authors to suspect a more diffuse cortical dysfunction than the nodular heterotopia revealed on magnetic resonance imaging.     

Electroencephalographic recordings of focal seizures in patients affected by periventricular nodular heterotopia: role of the heterotopic nodules in the genesis of epileptic discharges

Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia.     

双侧脑室旁结节状灰质异位症患者11例影像与临床研究

目的分析双侧脑室旁结节状灰质异位症（BPNH）的影像特征与所致癫癎的临床特点和疗效。方法MRI确诊的BPNH患者11例，根据是否合并其他神经系统解剖异常分为单纯BPNH组和叠加BPNH组，随访1～10年。对照分析2组患者的临床特点和药物治疗长期预后的差异。结果单纯BPNH组患者7例，发病年龄8～32岁，7例患者精神行为智力发育正常，癫癎发作均为部分性发作，4例有异位灰质结节部位的癎样放电，5例有发作间期的颞叶癎样放电，7例患者经卡马西平治疗均有效；叠加BPNH组患者4例，发病年龄3～8个月，均有早期的精神运动发育迟缓，癫癎发作频繁，存在抗癫癎药物抵抗。4例BPNH患者合并有心血管系统畸形。结论单纯BPNH组出现癫癎发作的年龄较叠加BPNH组晚，患者精神行为智力发育正常，发作形式均为部分性发作，对卡马西平治疗敏感，预后好。异位灰质结节部位和颞叶的癎样放电是单纯BPNH组患者的脑电图特征。应注意BPNH患者其他系统疾病的诊断，早期进行治疗。     

Developmental brain damage after chemically induced epileptic seizures.

25 Wistar rats were subjected twice daily to epileptic seizures induced by the convulsant gaz Flurothyl. Compared with littermates of the same sex and birth weight, the brain of seizure-treated rats showed a reduction of 6% (5.2 million cells) after 5 days and 17.6% (33.4 million cells) after 10 days of treatment.     

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

PurposePeriventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia.MethodsParticipants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality.Key findingsWe analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy.SignificanceA direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.     

Functional connectivity in brain networks underlying cognitive control in chronic cannabis users

The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes.     

Metabolic brain PET pattern underlying hyperkinetic seizures

This study aims to contribute to the identification of selective brain regions involved in hyperkinetic behaviors. We studied the whole-brain voxel-based interictal metabolic 18FDG-PET pattern of 23 patients with hyperkinetic seizures, in comparison with both 15 healthy subjects similar for age and gender, and 23 patients without hyperkinetic seizures. Patients were in particular similar for the localization of the epileptogenic zone, this having been defined using stereoelectroencephalography (SEEG) when clinically indicated (15/23 patients with hyperkinetic seizures and 13/23 patients without hyperkinetic seizures). Using conjunction voxel-based analysis, patients with hyperkinetic seizures exhibited significant hypometabolism within bilateral midbrain and the right caudate head, in comparison both to healthy subjects (p<0.05, FDR-corrected for the voxel) and to patients without hyperkinetic seizures (p<0.0167, uncorrected for the voxel). Findings were secondarily confirmed separately in each subgroup of patients with frontal, temporal or posterior epilepsy. These findings argue for a specific subcortical metabolic impairment in patients with hyperkinetic seizures, within brain structures supposed to be involved in the generation of primitive motor programs.     

主要表现为癫痫的脑海绵状血管瘤的治疗

目的探讨以癫痫为主要表现的脑海绵状血管瘤合理有效的治疗方法。方法收集我科2003年1月～2009年12月治疗的以癫痫为主要临床表现的脑海绵状血管瘤患者资料35例。单纯药物治疗组(17例):按照血药浓度检测结果进行药物剂量调整及换药,且全部病例疗程都在3年以上;手术联合药物治疗组(18例):严格根据癫痫手术要求进行术前评估及术中监测,切除致痫灶,术后继续使用抗癫药平均1年以上。对两组患者癫痫控制情况及抗癫药使用种类进行对比分析(平均随访2.9年)。结果手术联合药物治疗组患者有16例癫痫得到良好控制,药物治疗组仅6例得到控制(2=8.4777,P0.05),而且手术联合组较药物治疗组抗癫药使用种类明显减少。结论对于主要表现为癫痫的脑海绵状血管瘤手术联合药物比单纯药物治疗更有效。     

Gray matter volumes and cognitive ability in the epileptogenic brain malformation of periventricular nodular heterotopia

Periventricular nodular heterotopia (PNH) is a brain malformation clinically characterized by the triad of epilepsy, normal intelligence, and dyslexia. We investigated the structure–function relationship between cerebral volumes and cognitive ability in this disorder by studying 12 subjects with PNH and 6 controls using volumetric analysis of high-resolution anatomical MRI and neuropsychological testing. Total cerebral volumes and specific brain compartment volumes (gray matter, white matter, and cerebrospinal fluid) in subjects with PNH were comparable to those in controls. There was a negative correlation between heterotopic gray matter volume and cortical gray matter volume. Cerebral and cortical volumes in PNH did not correlate with Full Scale IQ, unlike in normal individuals. Our findings support the idea that heterotopic nodules contain misplaced neurons that would normally have migrated to the cortex, and suggest that structural correlates of normal cognitive ability may be different in the setting of neuronal migration failure.     

立体脑电图引导射频热凝毁损治疗脑室旁结节状灰质异位相关癫痫

目的探讨立体脑电图(SEEG)引导下的射频热凝毁损技术在治疗脑室旁结节状灰质异位相关癫痫中的作用。方法回顾性分析2015年3月至2017年5月北京丰台医院神经外科收治的5例脑室旁结节状灰质异位相关癫痫患者的临床资料。所有患者均根据症状学、头皮脑电图表现及影像学检查结果设计SEEG电极的植入方案,并行视频脑电监测,根据SEEG发作间期和发作期放电情况明确致痫灶的分布,根据其结果采用SEEG电极行射频热凝毁损术。术后通过门诊或电话进行随访,采用Engel分级进行预后评估。结果5例患者共植入23根电极,植入后未见明显并发症。随访时间为9~27个月,其中4例癫痫发作消失(Engel分级Ⅰ级),1例毁损术后发作频率无明显改善(Engel分级Ⅳ级)。所有患者在射频热凝毁损术中、术后均未出现明显不良反应。结论立体定向脑电图(SEEG)引导下的射频热凝毁损技术对治疗脑室旁结节状灰质异位相关癫痫具有重要的临床应用价值。     

Endogenous serum albumin content in brain after short-lasting epileptic seizures

Epileptic seizures can transiently alter the blood-brain barrier. We have determined the content of extravasated endogenous serum albumin in the brain and its change with time after bicuculline (0.3 mg/kg) induced epileptic seizures of a few minutes' duration in conscious rats. The brains were perfused with saline in situ 5 min, 2 h, 24 h, 3 or 7 days after the injection of bicuculline. The content of endogenous serum albumin in the cerebral cortex, diencephalon, mesencephalon, pons and cerebellum was determined by rocket immunoelectrophoresis. At 5 min the extravasation was most marked in the diencephalon with levels above 99% of the confidence limit of control brains in 8 out of 9 brains. Higher levels were seen at 2 h than at 5 min in the cerebral cortex and the cerebellum. Since it is known that the barrier rapidly normalizes after seizures, these findings suggest redistribution probably along clearance pathways into the cerebrospinal fluid (CSF) and possibly re-entry of albumin into the parenchyma from the CSF. Four out of 6 rats still had increased albumin levels in the cerebral cortex at 24 h. At 72 h and 7 days no values differed from controls.