Event-related fMRI of myoclonic jerks arising from dysplastic cortex

BACKGROUND: Malformations of cortical development can cause epileptiform activity and myoclonic jerks, yet EEG correlates of jerks can be difficult to obtain. METHODS: We studied a woman who had frequent episodes of persistent right-foot jerking since childhood. Ictal and interictal EEG had shown no localizing epileptiform activity. Functional imaging experiments were performed with concurrent video monitoring to document the timing of foot jerks. These studies mapped brain regions controlling voluntary right- and left-foot movements, and spontaneous right-foot jerks. RESULTS: High-resolution structural MR imaging revealed a dysplastic gyrus extending anteriorly off the left central sulcus. Event-related analysis of spontaneous jerks revealed prominent activation of the left precentral gyrus (right-foot motor area), bilateral medial frontal regions (supplementary motor area), and the dysplastic gyrus. Hemodynamic response modeling to foot jerks revealed the hemodynamic response peaked earlier in the dysplastic cortex and SMA regions than in the foot area. DISCUSSION: Event-related fMRI in a patient with spontaneous and induced epileptic foot jerks revealed brain regions active during jerks. The results of this analysis allowed us to tailor subsequent intracerebral recordings. Analysis of the timing of the hemodynamic response showed certain brain regions with an earlier rise in BOLD signal, suggesting a possible initiating role, or different hemodynamic response functions. Hemodynamic response timing should be considered carefully when interpreting event-related studies of epileptiform activity.     

Ganglioglioma arising from olfactory sheath: A rare site of an uncommon tumor

Gangliogliomas are rare slow growing tumors with a mixed population of dysplastic ganglion cells and glial components, reported at variable sites within the central nervous system, including the frontal, parietal and occipital lobes, the striatum, cerebellum, pituitary and pineal glands as well as the spinal cord. Rarely gangliogliomas have been reported arising within the cranial nerves, including the optic and trigeminal nerve. We present the first patient, to our knowledge, where such a tumor originated from the olfactory sheath. Migration defects leading to entrapment of sensory neurons during development is believed to be responsible for the pathogenesis of these lesions. The extent of surgical extirpation and histopathological anaplasia are important prognosticators. While gangliogliomas are rare tumors, it is crucial to consider them in the differential diagnosis of non-enhancing, poorly localized lesions along the cranial nerves.     

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.     

皮质发育不良大鼠脑皮质中尿激酶型纤溶酶原激活剂受体的表达

目的观察γ-射线照射诱导的皮质发育不良(CD)模型大鼠皮质尿激酶型纤溶酶原激活剂受体(uPAR)的表达,探讨其在癫痫发病机制中的作用。方法建立CD模型,按大鼠的不同年龄分为新生组、幼年组(又分为2周龄和4周龄)和成年组(2.5个月龄)。分别利用苏木精-伊红染色、免疫组化及免疫荧光染色,光镜下观察不同组之间大脑皮质的病理变化及uPAR阳性细胞表达的情况。结果免疫组化显示各组中均有uPAR阳性表达细胞;随着年龄的增长,阳性表达细胞逐渐减少,但CD模型组阳性表达细胞在皮层中所占比例明显高于正常对照组;免疫荧光双标显示uPAR阳性表达细胞主要是神经元。结论uPAR在CD发病过程中对神经组织的迁移发挥着关键作用,而较高比例的阳性神经元表达可能在CD致癫过程中发挥着重要作用。     

脑干神经节胶质细胞瘤

目的：探讨脑干神经节胶质细胞瘤的临床特点和手术治疗。方法：在我们手术治疗并经病理证实的560例脑干占位病变中，有4例神经节胶质细胞瘤，复习献中报道的24例进行临床分析。结果：脑干神经节胶质细胞瘤的主要发生在儿童及青年人，多位于延髓背部。其生长极为缓慢，病史长，顺MRI上显示为限局性肿瘤影像，显强化，可有囊变及钙化。4例中，1例肿瘤大部分切除，其余3例均完全切除。本组无死亡。结论：在不增加功能障碍的情况下，可将肿瘤完全切除；否则，行部分切除，必要时加行脑室分流手术，也能显延长患生存期。该病不需常规放疗。     

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.     

Cerebellar Ganglioglioma

The location of ganglioglioma (GG) within the infratentorial compartment is unusual. The authors report a rare case of GG in the cerebellar hemisphere. A 12-year-old boy suffered from headache and gait disturbance. Neuroimaging studies demonstrated a large enhancing cerebellar mass with cystic components compressing the forth ventricle. After complete resection of the tumor, the patient became symptom free. Histological examination on the tumor disclosed glial cells and dysplastic ganglion cells. Although it is a rare tumor, in the appropriate clinical setting, a GG should be considered in the presence of a cerebellar mass with both solid and cystic components on magnetic resonance images in children.     

神经节细胞胶质瘤伴癫痫21例临床分析

目的分析神经节细胞胶质瘤并癫痫的临床特点及影响发作控制结果的因素,并探讨其手术治疗策略。方法回顾2007年至2010年间21例神经节细胞胶质瘤并癫痫患者的临床资料,并统计分析各因素对发作控制结果的影响。结果 21例中,病变手术全切除17例,大部切除4例。10例联合癫痫灶处理。术后3例肢体轻偏瘫,1例部分性视野缺损。发作控制:EngleⅠ级15例,Ⅱ级4例,Ⅲ级1例,Ⅳ级1例。术后无发作(EngleⅠ级)与性别、病变是否全切相关,而与起病年龄、病程、发作类型、是否位于颞叶、是否难治性、病理级别、手术方式(单纯切除还是结合癫痫灶处理)等无明显相关性。结论对神经节细胞胶质瘤伴癫痫患者,应在保障安全前提下尽可能全切,必要时结合神经导航、术中唤醒皮层电刺激功能区定位或颅内电极等技术,对顽固性癫痫应同时处理癫痫灶;神经节细胞胶质瘤手术后发作控制相对良好。     

Alterations of Phosphatidylinositol 3-Kinase Pathway Components in Epilepsy-associated Glioneuronal Lesions

Summary:  Low-grade glioneuronal lesions involving tumors such as gangliogliomas and focal cortical dysplasias (FCD) predispose individuals to pharmacoresistant epilepsy. A frequent variant of FCD is composed of dysplastic cytomegalic neurons and Taylor-type balloon cells (FCD_IIb). Those are similar to cellular elements, which are present in cortical tubers in the autosomal dominant inherited tuberous sclerosis complex (TSC). This phacomatosis is caused by mutations in the TSC1 or TSC2 genes. Recent data have indicated accumulation of distinct allelic variants of TSC1 also in FCD_IIb. TSC1 represents a key factor in the phosphatidylinositol 3-kinase (PI3K) pathway. A variety of alterations in the PI3K-pathway have been recently reported in epilepsy-associated glioneuronal malformations. Here, we discuss pathogenetic similarities and differences between cortical dysplasias as well epilepsy-associated glioneuronal tumors and TSC-associated cortical tubers with a focus on PI3K-pathway components including ezrin, radixin and moesin (ERM), which represent downstream effectors involved in cytoskeleton-membrane interference. No evidence has been found for mutational events of ERM genes to play a major pathogenetic role in epilepsy-associated glioneuronal malformations. In contrast, aberrant expression of ERM proteins in FCDs and gangliogliomas was observed. These alterations may relate to compromised interactions of dysplastic cellular components in epilepsy-associated glioneuronal lesions and be involved in aberrant PI3K-pathway signaling in epilepsy-associated malformations. However, the underlying cause of PI3K-pathway activation and the functional relationship of PI3K-pathway activity to generation of seizures in epilepsy-associated glioneuronal lesions will need to be determined in the future.     

Ganglioglioma arising in a Peutz-Jeghers patient: a case report with molecular implications

The Peutz-Jeghers syndrome (PJS), an autosomal dominant disorder caused by inactivating germline mutations in the serine–threonine kinase gene LKB1, is characterized by mucocutaneous pigmentation, multiple gastrointestinal hamartomatous polyps, and by an increased risk for developing tumors involving several different organs. To date, no brain tumors have been described in PJS patients. In this report, we describe a case of ganglioglioma in a 22-year-old PJS patient. Single-strand conformation polymorphism-Heteroduplex analysis evidenced an abnormal pattern in exon 6 of the LKB1 gene. Sequencing revealed a 821delTinsAC mutation creating a termination codon 29 nucleotides downstream (p.Asn274fsX11). RNA studies showed an out-of-frame LKB1 isoform derived from the wild type allele and generated by exon 4 skipping. Since the LKB1 gene is expressed in the fetal and adult brain, our data would suggest its likely involvement in the pathogenesis of a subset of gangliogliomas.     

FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic tubers and cortex in patients with tuberous sclerosis complex: a preliminary report

PURPOSE: Patients with tuberous sclerosis complex (TSC) are potential surgical candidates if the epileptogenic region(s) can be accurately identified. This retrospective study determined whether FDG-PET/MRI coregistration and diffusion-tensor imaging (DTI) showed better accuracy in the localization of epileptogenic cortex than structural MRI in TSC patients. METHODS: FDG-PET/MRI coregistration and/or DTI for apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were utilized in 15 TSC patients. Presurgery scalp EEG and postsurgery seizure control identified epileptogenic tubers (n = 27) and these were compared with nonepileptogenic tubers (n = 204) for MRI tuber volume, volume of FDG-PET hypometabolism on MRI coregistration, DTI, ADC, and FA values. RESULTS: Compared with nonepileptogenic tubers, epileptogenic regions had increased volume of FDG-PET hypometabolism (p < 0.0001), and increased ADC values in subtuber white matter (p < 0.0001). In contrast, the largest MRI identified tuber (p = 0.046) and decreased FA values (p = 0.58) were less accurate in identifying epileptogenic regions. Larger volumes of FDG-PET hypometabolism correlated positively with increased ADC values (p = 0.029), and localized to areas of cortical dysplasia adjacent to the tuber in four cases. CONCLUSIONS: Larger volumes of FDG-PET hypometabolism relative to MRI tuber size and higher ADC values identified epileptogenic tubers and adjoining cortex containing cortical dysplasia in TSC patients with improved accuracy compared with largest tuber by MRI or lowest FA values. Used in conjunction with ictal scalp EEG and interictal magnetoencephalography, these newer neuroimaging techniques should improve the noninvasive evaluation of TSC patients with intractable epilepsy in distinguishing epileptogenic sites for surgical resection.     

Synaptogenesis in hemimegalencephaly: the numerical density of asymmetric and symmetric synapses in the cerebral cortex

Specimens of cerebral cortex were prepared for electron microscopy from cortical resections performed for the treatment of intractable seizures in four cases of hemimegalencephaly (HME). Morphometric analyses were performed to determine mean cortical thickness, the numerical density of synapses (N _V, contacts per mm³) and the number of synapses in a column of cortex beneath 1 mm² of pial surface. The N _V were calculated separately for asymmetric and symmetric synapses as well as for axospinous, axodendritic and axosomatic contacts. Four cases of Rasmussen’s encephalitis served as controls, with tissue being sampled from a region distant to the site of the inflammatory lesion without obvious necrosis. The N _V of synapses did not differ significantly between HME cases and controls. The proportions or asymmetric and symmetric synapses were similar in both groups, as were the proportions of axospinous, axodendritic and axosomatic contacts. However, there was a significant increase in mean cortical thickness in HME cases (130%, P < 0.05). Consequently, there was a significant increase in the total number of synapses in a column of cortex (126%, P < 0.05). In HME the cerebral cortex is characterized by synaptic dysgenesis. Although synaptic density per unit volume of tissue appears relatively normal, the increased thickness and volume of the cerebral cortex provides for an increase in the total number of synapses in a given cytoarchitectonic area. Received: 31 October 1995 / Revised, Accepted: 5 February 1996     

Focal brain malformations: Seizures, signaling, sequencing

Focal malformations of cortical development are highly associated with intractable epilepsy in children and adults. Most patients with focal cortical malformations and epilepsy will require epilepsy surgery. Recent studies have provided new insights into the developmental pathogenesis of cortical malformations specifically relating to alterations in cell signaling though the mammalian target of rapamycin (mTOR) pathway. Focal cortical dysplasias, hemimegalencephaly, and tubers in tuberous sclerosis complex all exhibit evidence for hyperactive mTOR signaling, suggesting that these disorders form a spectrum of malformations or "TORopathies" characterized by disorganized cortical lamination, cytomegaly, and intractable seizures. Alterations in mTOR activity in focal brain malformations provide a potential pathogenic pathway to investigate for gene mutations and to exploit for animal models. Most importantly, however, if select focal cortical malformations result from enhanced mTOR signaling, new therapeutic antiepileptic compounds, such as rapamycin, can be designed and tested that specifically target mTOR signaling.     

Histopathological Correlates of Epileptogenicity as Expressed by Electrocorticographic Spiking and Seizure Frequency

Summary: Purpose : To study the correlation between histopathology and epileptogenicity, as measured by seizure frequency and electrocorticography (EcoG), in patients with cortical dysplasia (CD) as compared with control patients with gangliogliomas or gliomas.
Methods : The influence of the histopathological classification and the presence of balloon cells in CD on the frequency and extension of five predefined patterns of ECoG spiking, seizure frequency, age of seizure onset and 6-month postoperative outcome were analyzed in 32 patients with focal epilepsy undergoing presurgical evaluation with chronically implanted subdural electrodes.
Results : Comparison of patients with CD, gangliogliomas, and gliomas showed that the seizure frequency was greatest in patients with CD and ECoG spiking and was most extensive in patients with gangliogliomas. The onset of epilepsy was earlier in patients with CD and with gangliogliomas. None of these differences was significant. However, in patients with CD, the presence of balloon cells was associated with significantly greater seizure frequency (p = 0.009), and a significantly greater number of electrodes recording continuous frequent spiking (p = 0.03). The presence of continuous very frequent spiking correlated with the duration of the epilepsy and the number of seizures recorded during monitoring. No significant correlation was detected between histopathology, seizure frequency, or ECoG activity and postoperative outcome, which was relatively favorable in patients with balloon cells.
Conclusions : CD refers to a variety of histopathological patterns associated with different epileptogenicity. In CD, increased clinical and ECoG epileptogenicity correlates with the presence of balloon cells. This finding confirms that balloon cells should be considered in the histopathological classification of CD. The predefined ECoG were not specific for any of the histopathologies investigated.     

Ganglioglioma in Brainstem : Case Report and a Review of Literatures

Ganglioglioma is an infrequent tumor of the central nervous system (CNS); mostly supratentorial region. But, they can occur anywhere in the central nervous system such as brainstem, cerebellopontine angle (CPA), thalamus, optic nerve and spinal cord. Although it occurs rarely, ganglioglioma should be included in the differential diagnosis of a posterior fossa mass because early recognition is important for treatment and patient counseling.     

不同病理分型局部脑皮质发育不良的MRI研究

目的 探讨不同病理分型局部脑皮质发育不良(FCD)在MRI表现上的特点.方法 回顾性分析广州医学院第二附属医院自2006年5月至2010年6月收治的23例FCD患者资料.所有患者均经手术病理证实,按Palmini方法FCDⅠA、FCDⅠB、FCDⅡA、FCDⅡB4型,总结各类型患者MRI表现的特点.结果 23例患者中FCD Ⅰ A 2例,FeD Ⅰ B 6例,FCDⅡA 8例,FCDⅡB7例.FCDⅡ型中,有11例MRI表现为病灶Flair高信号,Ⅰ型中仅有2例,差异有统计学意义(P=0.039).而病灶T2高信号、白质内向脑室延伸带等表现虽然在Ⅰ、Ⅱ型间相差较大,但差异没有统计学意义(P=0.074、0.058).ⅡB型的MRI表现在灰白质分界不清、病灶T2高信号、脑沟加深、灰质增厚、白质内向脑室延伸带等方面均明显高于其他3型,差异有统计学意义(P<0.05).结论 不同病理分型FeD的MRI表现各有特点,特别是ⅡB型,其在MRI上的表现与其他3型明显不同,了解这些特点有助于FCD的早期诊断和术前评估.     

Focal cortical dysplasias in eloquent cortex: functional characteristics and correlation with MRI and histopathologic changes

PURPOSE: Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features. METHODS: Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics. RESULTS: Language or motor areas were colocalized with epileptogenic regions (n=6 of 8, 75%), but were not mapped in regions of increased signal on fluid-attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n=5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells. CONCLUSIONS: We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.