Focal cortical dysplasia with calcification: a case report

Case report Focal cortical dysplasia (FCD) with calcification is rare. We presented a 13-year-old epileptic patient with FCD and calcification in the left frontal lobe. At age 24, the FCD lesion and the surrounding epileptogenic cortex and underlying subcortex were removed after chronic subdural electrode recording. Histological examination showed that the calcified lesion was not independent of the FCD lesion but located in the subcortical area of the FCD lesion. A neoplastic nature was ruled out for the lesion. Discussion The pathophysiological mechanism involved in the coexistence of FCD and calcification is discussed.     

Focal cortical dysplasia of Taylor's balloon cell type: a clinicopathological entity with characteristic neuroimaging and histopathological features, and favorable postsurgical outcome

BACKGROUND AND PURPOSE: Focal cortical dysplasia of Taylor's balloon-cell type (FCD-BC) are a frequent cause of pharmacoresistant epilepsy in young patients. In order to characterize FCD-BC, we coupled MRI and histopathology, and analyzed the clinical outcome following epilepsy surgery. METHODS: From an epilepsy data bank with 547 histological specimens, 17 FCD-BC were re-evaluated of which high resolution MRI was available. Five additional FCD-BC were prospectively identified by MRI. Histopathological and immunohistochemical features were related to MRI. Outcome following lesionectomy was analyzed as determined on routine examinations 3, 6 and 12 months following surgery. RESULTS: All but one lesion were located outside the temporal lobe. A markedly hyperintense funnel-shaped subcortical zone tapering towards the lateral ventricle was the characteristic finding on FLAIR MRI. Histopathologically, the subcortical zone of the FCD-BC displayed hypomyelinated white matter with radially oriented balloon cells and gliosis. Dysplastic neurons were found in the adjacent, disorganized cortex. All patients with complete lesionectomy were seizure free one year following surgery. CONCLUSION: Focal cortical dysplasias of Taylor's balloon-cell type (FCD-BC) have characteristic MRI and histopathological findings. MRI recognition is important, since outcome following resective surgery is favorable.     

Rud syndrome with focal cortical dysplasia: a case report

We report a female patient with ichthyosis, epilepsy, mental retardation, hypergonadotrophic hypogonadism, polyneuropathy, and cranial dysmorphisms. This clinical picture may satisfy the main diagnostic criteria that characterize Rud syndrome (RS), a rare neurocutaneous disease. The patient underwent extensive clinical evaluation, neurophysiological studies (wakefulness and sleep EEG, EMG), dermatological and endocrinological evaluation and neuroimaging study (3 Tesla brain MRI). Interestingly, brain MRI unveiled a malformation of cortical development, never reported previously in RS. Although seizure semiology and EEG features could not provide clear cut information suggesting a focal onset, the role of this MRI finding in the genesis of the epileptic seizures cannot be ruled out. The finding of a focal cortical dysplasia in RS might be related to genetic abnormalities affecting the development of both epidermis and neural structures with the same embryological origin.     

局灶性皮质发育不良皮质中NMDA受体亚基表达情况

目的探讨N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体亚基NR1、NR2A、NR2B在难治性癫病人局灶性皮质发育不良(focal cortical dysplasia,FCD)皮质中的表达及意义。方法选取20例难治性颞叶癫(术后病理证实为FCD)为FCD组及10例颞叶血管畸形病人为对照组,收集两组病人术中切除的颞叶皮质,利用免疫组化和Syber Green荧光定量PCR技术检测标本中NMDA受体亚基NR1、NR2A、NR2B蛋白和mRNA的表达情况。结果对照组NR1、NR2A和NR2B蛋白表达分别为3.5、3、3,FCD组分别为5、5、5。对照组NR1、NR2A和NR2B mRNA表达分别为1.109、1.079、1.157,FCD组分别为2.176、2.324、2.348。与对照组比较,FCD组NR1、NR2A、NR2B蛋白和mRNA表达显著增加(均P<0.01)。结论 FCD皮质中NMDA受体亚基蛋白及mRNA表达升高,可能是FCD致机制之一。     

Efficacy of sirolimus for epileptic seizures in childhood associated with focal cortical dysplasia type II

ObjectiveThe efficacy of the mechanistic target of rapamycin inhibitor, sirolimus, was recently reported for patients more than 6 years of age by Kato et al. We evaluated the efficacy and safety of sirolimus in a 2-year-old patient with recurrent focal seizures with impaired consciousness after focal cortical dysplasia (FCD) type IIa resection.MethodsThe patient was a 2-year-old girl who had recurrent seizures after undergoing FCD resection at 4 months of age. The initial dose of sirolimus was 0.5 mg/day and was gradually increased using the trough blood concentration before oral administration as an index, and evaluation was performed at 92 weeks.ResultsThe trough blood level of sirolimus was increased to 6.1 ng/mL and maintenance therapy was started at 40 weeks. Focal seizures with impairment of consciousness with tonic extension of the limbs decreased. No critically serious adverse events occurred.ConclusionSirolimus was effective against epileptic seizures from FCD type II even for a child under 5 years of age. There were no critically serious adverse events and administration could be continued.     

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.     

Immunohistochemical expression of Trk receptor proteins in focal cortical dysplasia with intractable epilepsy

Focal cortical dysplasia (FCD), which is often associated with intractable epilepsy, is a form of abnormal structure of the cerebral cortex caused by a disorder of normal neocortical development. In such cerebral lesions obtained from four patients (two male, two female; average age 32.3 years at operation), the immunohistochemical expression of Trk receptors, which interact with neurotrophins and result in both growth and maturational changes in neuronal cells, was investigated in relation to the possible histogenesis of these lesions. In all cases, a derangement of the cortical laminar structure, dysplastic cytomegalic neurones, and large round balloon cells were the characteristic histological features. Immunohistochemically, the TrkA expression was localized in large dysplastic cytomegalic neurones, and TrkB expression was observed in large dysplastic and relatively small neuronal cells within the affected cortex. Although the exact roles of neurotrophins and their receptors in the pathogenesis of FCD remain uncertain, its development might be governed by such neurotrophic influences, and thus possibly prevent the death of abnormal neuronal cells. In addition, Trk receptors in FCDs may also play a role in establishing in the intrinsic epileptogenicity of FCDs.     

大脑半球弥漫性星形细胞瘤的临床、影像学和病理特征(附1例报告)

目的 探讨大脑半球弥漫性星形细胞瘤(DA)的临床、影像学和病理特征.方法 回顾分析1例DA患者的临床资料.结果 本例临床表现为头晕、头痛、呕吐、记忆力、计算力减退等.头部CT示左侧额、顶部脑白质区密度降低,范围广,侧脑室体部受压中线略向右移,脑沟裂池消失.MRI显示左颞、顶叶大片长T1、长T2异常信号,信号强度欠均匀,病灶境界不清,左侧脑室受压变小中线右移.病理检查见脑灰白质中星形细胞散在分布,细胞密度略多于正常脑组织,可见单核和小多核巨细胞、卫星现象、血管内皮增生,偶见核丝分裂相,瘤细胞磷钨酸苏木精染色(PTAH)( ),胶质纤维酸性蛋白(GFAP)强阳性,S-100、α-抗糜蛋白酶阳性,铁蛋白局灶阳性,波纹蛋白和神经元特异性稀醇化酶均为阴性.电镜见肿瘤细胞的突起有大量胶质丝.结论 大脑DA的临床和影像学表现以高颅压征、大脑弥漫性病变为特征;病理学检查是诊断DA的主要依据;本病手术治疗的效果不好.     

局灶皮层发育不良致难治性癫痫160例临床病理分析

目的探讨局灶皮层发育不良的临床病理学分型及特点。方法收集160例病理诊断为局灶皮层发育不良的难治性癫痫手术治疗患者的病理标本及临床资料。采用HE和免疫组织化学染色,探讨各种类型癫痫病理的临床病理学特点。结果局灶皮层发育不良160例,其中FCDⅠB134例、FCDⅡA16例、FCDⅡB10例。结论局灶皮层发育不良为引发难治性癫痫最常见病因,而亚型中以FCDⅠB型最为多见。免疫组化有助于FCD的诊断与分型。     

Ictal SPECT is useful in localizing the epileptogenic zone in infants with cortical dysplasia

Aims. To assess the localizing value of ictal SPECT in very young epilepsy surgery candidates when cerebral haemodynamic responses are known to be immature. Methods. We retrospectively studied 13 infants with intractable focal epilepsy caused by focal cortical dysplasia (FCD). Completeness of resection of the (1) ictal SPECT hyperperfusion zone and (2) cerebral cortex with prominent ictal and interictal abnormalities on intracranial EEG (ECoG or long‐term invasive monitoring) and the MRI lesion, when present, were correlated with postoperative seizure outcome. Results. All five patients with complete resection of the ictal SPECT hyperperfusion zone were seizure‐free compared to only one of eight patients with incomplete or no excision of hyperperfusion zones (p=0.00843). Similar results were noted for the MRI/iEEG‐defined epileptogenic region; five of six patients with complete removal were seizure‐free, whereas only one of seven incompletely resected patients was seizure‐free (p=0.02914). All four patients who underwent complete resection of both regions were seizure‐free compared to none of the six with incomplete resection (p=0.01179). Conclusion. Despite age‐related differences in cerebral perfusion, ictal SPECT provides useful localization data in infants with FCD. Complete resection of the hyperperfused regions is a strong predictor of favourable outcome. The added information may alleviate the need for invasive EEG evaluations in some patients.     

Clinical and experimental studies of epilepsy associated with focal cortical dysplasia

The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.     

局灶性皮质发育不良相关癫痫的诊疗进展

局灶性皮质发育不良（FCD）是临床中常见的局灶性癫痫的病理类型之一,多数FCD患者在癫痫起病后即表现出耐药性,成为难治性癫痫。2011年国际抗癫痫联盟提出了新的FCD病理分型后,让大家对FCD有了更进一步的认识。近几年随着医学检测技术、病理研究及神经影像技术的发展,针对不同病理亚型的研究使得临床医生对FCD致病机制及治疗措施的决策有了新的理解。该文综合近年相关文献,对FCD不同亚型临床特点、治疗方法及相关预后作一综述,以期为临床决策提供帮助。     

ILAE focal cortical dysplasia type IIIc in the ictal onset zone in epileptic patients with solitary meningioangiomatosis

“Solitary” meningioangiomatosis (MA) is a rare, benign, hamartomatous lesion of the cerebral cortex and frequently leads to epilepsy. However, the source of the epileptogenicity in meningioangiomatosis remains controversial. We report two surgically‐treated meningioangiomatosis cases with medically intractable epilepsy. In both cases, chronic subdural electrocorticogram (ECoG) recordings identified the ictal onset zone on apparently normal cortex, adjacent to and/or above the meningioangiomatosis lesion, not on the meningioangiomatosis lesion itself. The ictal onset zone was resected, along with the MA lesion, and good seizure outcome was achieved. Histological examination of the ictal onset zone revealed the presence of ILAE focal cortical dysplasia (FCD) type IIIc. Our case studies suggest that in the surgical management of epilepsy with meningioangiomatosis, it is important to identify undetected, but epileptogenic, ILAE FCD Type IIIc, using preoperative multimodal examinations, including chronic ECoG recordings.     

Focal cortical dysplasia II-related seizures originate from the bottom of the dysplastic sulcus: A stereoelectroencephalography study

ObjectivesFocal cortical dysplasia (FCD) II is a frequently observed histopathological substrate in epilepsy surgery. In the present study, we explored the spatial distribution of epileptogenic activities across FCD II lesions using stereoelectroencephalography.MethodsPatients with histopathologically confirmed type II FCDs and who had at least one depth electrode that go through the wall of the dysplastic sulcus from the surface to the bottom were included. The dysplastic sulci were divided into the bottom and non-bottom parts manually, and contacts were defined as bottom or non-bottom contacts according to their locations. Factors (bottom location, pathological subtype, magnetic resonance imaging manifestation, and presence of bottom-of-sulcus dysplasia) potentially associated with earliest onset identified by conventional visual analysis, epileptogenicity index (EI), and standardized number of high-frequency oscillations (HFOs) were analyzed. Linear regression analyses between distance (from the location of the analyzed contact to the bottom of the sulcus) and EI value and HFO number were performed.ResultsSixteen patients with 19 depth electrodes containing 112 valid contacts were included. Bottom location was the sole factor significantly associated with earliest onset (P < 0.001), EI value (P < 0.001), and HFO number (P < 0.001). Most earliest onsets were recorded by the bottom contacts, bottom contacts had higher EI value (0.81 ± 0.28 vs. 0.31 ± 0.24, P < 0.001) and more HFOs (0.78 ± 0.28 vs. 0.35 ± 0.31, P < 0.001) than non-bottom contacts. Moreover, the EI value (R = −0.72, P < 0.001) and HFO number (R = −0.64, P < 0.001) were significantly negatively correlated with distance, regardless of histopathological subtype, MRI manifestation, or absence of bottom-of-sulcus dysplasia.ConclusionSeizure onsets and interictal HFOs most often arise from the bottom part of a sulcus with type II FCD.SignificanceThe findings of the present study contribute to intracranial electrode selection, trajectory planning, and, later on, resection of this kind of malformation.     

Pilocytic astrocytoma presenting as primary diffuse leptomeningeal gliomatosis: report of a unique case and review of the literature

We describe a 25-year-old male patient with primary diffuse leptomeningeal gliomatosis (PDLG) presenting with gait ataxia, positive Lhermittes sign, double vision, and right abducens nerve palsy. Spinal magnetic resonance imaging showed extended intradural, extramedullary, contrast-enhancing masses with compression of the myelon. Spinal leptomeningeal biopsy revealed a pilocytic astrocytoma WHO grade I. Despite chemotherapy with vincristin and carboplatin, the patient died 2 months after admission. A thorough autopsy showed no evidence for primary neoplasms in brain, spine and optic nerve. Sequence analysis of tumor protein 53 gene (TP53) revealed a missense mutation in exon 5, and expression of phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) protein was not detected, which may have contributed to astrocytoma development. To our knowledge, this is the first definitive case of pilocytic astrocytoma presenting as PDLG.     

Focal cortical dysplasia: prevalence, clinical presentation and epilepsy in children and adults

Focal cortical dysplasias (FCD) are defined as circumscribed malformations of cortical development. They result from an impairment of neuronal proliferation, migration and differentiation. In the diagnosis of focal epilepsy FCD prevalence ranges between 5% and 25%, depending on patient collective and imaging techniques. Several 'cryptogenic' epilepsies may be caused by FCD but have not been diagnosed because of the lack of high-quality magnetic resonance imaging assessment. Retrospective analysis of patients who have undergone epilepsy surgery can be biased because of the fact that they represent a mere subset of potential FCD diagnoses. Epilepsy typically manifests within the first years of life, but has been documented up to the age of 60 years. Cognitive impairment commonly accompanies early onset. Epilepsy is often refractory to antiepileptic drug (AED) treatment. Clinical observations and pathophysiological findings illustrate intrinsic epileptogenicity. Upregulation of drug transporter proteins has been found in FCD tissue. There is no specific drug treatment in FCD, as any AED used in focal epilepsy could prove effective. A sequential AED therapy should be designed individually and take side effects as well as developmental progresses into consideration. Fifty to sixty-five percent of FCD patients are rendered seizure-free after surgery. Presurgical evaluation should be initiated after two unsuccessful AED trials. Both risks and potential benefits regarding seizure control and developmental impairment need to be considered on an individual basis when deciding between surgical intervention and conservative treatment. Current knowledge on epilepsy course and psychomotor development in FCD is limited in the absence of qualified long-term studies combining imaging with cognitive evaluation.     

Review: Mechanistic target of rapamycin (mTOR) pathway,focal cortical dysplasia and epilepsy

Over the last decade, there has been increasing evidence that hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is a hallmark of malformations of cortical development such as focal cortical dysplasia (FCD) or hemimegalencephaly. The mTOR pathway governs protein and lipid synthesis, cell growth and proliferation as well as metabolism and autophagy. The molecular genetic aetiology of mTOR hyperactivation has only been recently clarified. This article will review the current and still evolving genetic advances in the elucidation of the molecular basis of FCD. Activating somatic mutations in the MTOR gene are to date the most frequent mutations found in FCD brain specimens.