结节性硬化症癫痫的术前评估及手术方式的选择

目的 总结结节性硬化症所致癫痫患者的术前评估及手术方式,观察术后疗效.方法 回顾性分析北京三博脑科医院2004年6月至2011年6月手术治疗的20例结节性硬化症患者临床资料并系统随访1～5年.结果 经过综合评估,单纯致痫结节切除术8例;电极植入后致痫结节切除术1例;脑叶切除术4例;致痫结节切除+致痫皮层热灼术2例;脑叶切除+离断术1例;迷走神经刺激术2例;胼胝体全段切开术2例.术后随访Engel Ⅰ级11例,Ⅱ级2例,Ⅲ级5例,Ⅳ级2例,有效率达90％ (18/20).结论 经过精确术前评估,选择合适的手术方式,可以有效地控制或减轻结节性硬化引起的癫痫发作.     

Neurological manifestations of tuberous sclerosis complex

CNS lesions of tuberous sclerosis complex (TSC) are due to a developmental disorder of neurogenesis and neuronal migration. MRI studies provide excellent in vivo demonstration of the various pathologic lesions. Symptoms of cortical tubers may include seizures, mental retardation, learning disabilities, and abnormal behavior. Seizures have a focal or multifocal origin, this clinical feature depending on the localization of the cortical tubers. Epilepsy associated with TSC is often intractable, but seizure control has benefited from the introduction of the new antiepileptic drugs. Carefully selected drug-resistant patients can be assessed with intensive monitoring as candidates for surgical removal of epileptogenic lesions. The success of epilepsy surgery is predicated on the clear identification of epileptogenic foci.     

The ominous sequence in patients with tuberous sclerosis complex

Background: The clinical phenotypes and their severity in patients with tuberous sclerosis complex can be quite variable and are sometimes never determined simply by the primary mutation. These make clinically selecting appropriate treatments and predicting disease outcome difficult. In this report, the prognostic ominous sequence was evaluated in association with clinical manifestations and gene mutations. Methods: The patients were classified by each renal lesion of angiomyolipomas and polycystic disease. The other clinical manifestations and outcomes of epilepsy, mental retardation, facial angiofibromas, subependymal giant cell astrocytoma, cortical tubers were reviewed and each gene mutations were analyzed in seven unrelated patients. Results: Two patients with multiple and large proliferative renal angiomyolipoma showed poor clinical outcome than the patients with other renal lesions. These patients presented with progressively proliferative facial angiofibroma, West syndrome, Lennox–Gastaut syndrome, severe mental retardation, subependymal giant cell astrocytoma and they were affected by TSC2 gene mutations. Conclusion: The sequence of progressively proliferative renal angiomyolipoma, facial angiofibroma, West syndrome and TSC2 gene mutations might be prognostic ominous factors.     

Tumor growth in patients with tuberous sclerosis complex on the ketogenic diet

Purpose

New evidence is emerging that the availability of nutrients plays a key role in regulating the mammalian target of rapamycin complex-1 (mTORC1) signaling pathway in human cancers. Tuberous sclerosis complex (TSC) is a genetic disorder which results in the growth of hamartomatous lesions in multiple organs due to insufficient suppression of the mTORC1 pathway. A minority of patients with TSC who develop epilepsy which is intractable to standard anticonvulsant medical and/or surgical treatments are treated with the ketogenic diet. To provide insight into the effects of nutrient manipulation on tumor growth in this condition, we describe our experience in a unique group of patients with known tuberous sclerosis complex who are on the ketogenic diet for seizure control. Methods: A retrospective chart review was performed of patients with TSC treated with the ketogenic diet between January 2002 and May 2007 at Massachusetts General Hospital. Results: Five patients with definite TSC underwent serial imaging for tumor growth while on the ketogenic diet or had unchanged imaging prior to the onset of the diet and after termination. Three out of five patients, all children, had progression of a known tumor or tumors or the development of a new tumor while on the ketogenic diet. Conclusion: In this limited case series of five TSC patients, the ketogenic diet did not induce tumor regression or suppress the growth of TSC-related tumors.     

Epilepsy surgery in tuberous sclerosis complex: early predictive elements and outcome

Aim  The aim of the study was to evaluate the surgical treatment of epilepsy and detection of possible early surgery predictive elements in patients with tuberous sclerosis complex (TSC). Materials and methods  Forty-two TSC patients with epilepsy were selected and divided into two main groups: definite and fruste forms. Definite forms were divided into different groups: patients with pharmacologically controlled epilepsy, patients with pharmacoresistant epilepsy excluded from surgery after an extensive presurgical assessment, and patients with a pharmacoresistant epilepsy who underwent surgery. We compared the definite TSC groups to identify elements that predict surgical candidacy. Second, we compared all operated patients to assess surgical outcome. Conclusion  We found several factors that could predict a surgical intervention even if identification of patients with refractory epilepsy who can benefit from surgery is an evolving process. Also, several positive factors for good surgical outcome were identified. Patients with the fruste form had excellent surgical outcome.     

54例结节性硬化症神经系统损害临床分析

目的分析结节性硬化症神经系统损害特点。方法应用癫痫严重程度量表和韦氏量表分析54例结节性硬化症患者癫痫、智能障碍特点。结果癫痫发生率89%(48/54);84%患者10岁前发生癫痫,1岁以内为首发癫痫高峰;智力障碍者占63.3%。结论结节性硬化症患者癫痫发生率高、发病年龄早、发作频繁,智力障碍常见。     

结节性硬化症TSC2基因突变的分析

目的 分析结节性硬化症(TSC)致病基因TSC2突变方式.方法 采用聚合酶链反应-单链象多态性(PCR-SSCP)技术,对TSC一家系4例TSC患者(其中1例疑似)、1例散发性TSC患者外周血TSC2的41个外显子进行检测,并与家系中健康对照组和无血缘关系健康对照组进行比较.结果 此1家系中4例TSC患者(包括1例疑似)的TSC2基因外显子33发生了1346丝氨酸(S)→脯氨酸(P)(4037T→C)错义突变,1例散发性TSC患者及两健康对照组未检测到TSC2基因突变.结论 在TSC患者中TSC2外显子33错义突变(1346S→P,4037T→C)是一种尚未报道的新发现的基因突变方式.     

手术治疗结节性硬化的疗效观察

目的 探讨手术治疗结节性硬化引起癫痫的疗效.方法 回顾性分析6例患者的临床资料并系统随访18-30个月,综合评估3例导航下行致痫结节切除+皮层低功率热灼术;2例皮层电极植入后,经过监测,行致痫结节切除+皮层热灼术;1例行胼胝体前段切开术的疗效.结果 癫痫发作完全消失2例(Engel Ⅰ级),偶有发作1例(Engel Ⅱ级),发作减轻3例(Engel Ⅲ级).结论 手术可以有效地控制或者减轻结节性硬化引起的癫痫发作.     

伴有癫痫发作的结节性硬化症患者的脑电图特点

目的分析伴有癫痫发作的结节性硬化症(TSC)患者的脑电图特点。方法总结101例有痫性发作的TSC患者的临床资料,对其发作间期及发作期脑电图进行分析。结果癫痫的发病年龄从10d～28岁不等,3岁以内发病者68人(67%)。101例患者均行24h视频脑电图监测,3例脑电图正常,98例脑电图异常,其中3例存在高幅失律,23例为慢波背景活动,72例背景活动正常或接近正常,但其中11例患者脑电图可见较多慢活动。在有痉挛发作的13例患者中,3例脑电图背景为高幅失律,7例为慢波背景活动。发作间期显示痫样波在双侧均明显者35例,一侧痫样波明显者63例,主要集中在前头部。48例患者监测到发作,监测到的发作最常见为部分性发作(27例),26例可以明确起源,主要集中在额颞叶。结论大多数TSC患者脑电图异常,可见痫样波发放,54%TSC患者通过视频脑电图可以明确痫样波起源,主要在额颞叶,左右两侧无明显差异。     

The natural history of epilepsy in tuberous sclerosis complex

Background : Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease. Methods : A retrospective chart review of all patients with TSC seen between January 2002 and October 2008. Charts were reviewed for a history of infantile spasms (IS), seizure other than IS, refractory epilepsy, Lennox‐Gastaut syndrome (LGS), anticonvulsant medication use, ages of seizure onset, last seizure, last clinic visit, clinical seizure phenotype(s), cognitive impairment, and genetic mutation. Results : Two hundred ninety‐one patients were included. Among these patients, 37.8% had a history of IS; 85.2% had a history of seizure; 54.1% developed multiple seizure types, not including IS; 63.2% had seizure onset in the first year of life; and 12.1% of adults without a seizure history developed epilepsy. Of epilepsy patients, 62.5% developed refractory epilepsy and 33.5% achieved epilepsy remission; 37.5% of these patients achieved medication freedom. IS was a risk factor for refractory epilepsy (p<0.0001) and LGS (p<0.0001). History of seizure, IS, age at seizure onset, and refractory epilepsy each correlated with poor cognitive outcome (p<0.0001). Epilepsy remission correlated with better cognitive outcome (p<0.0001). TSC2 was a risk factor for IS and epilepsy; patients without an identified mutation were more likely to achieve remission. Conclusion : Most patients with TSC develop epilepsy and most develop multiple seizure types. Onset typically occurs in the first year of life; however, adults remain at risk. Although refractory epilepsy is common, many patients achieve seizure control. Many features of seizure history are predictive of cognitive and epilepsy outcome.     

结节性硬化症患者癫痫发作对智力的影响

目的 研究结节性硬化症(TSC)患者癫痫发作与智力的关系. 方法 采用回顾性分析方法总结南方医科大学南方医院及广东三九脑科医院自2007年5月至2012年5月收治的110例伴有癫痫发作的TSC患者资料,分析影响患者智力低下的因素. 结果 本组患者中男性67例,女性43例.癫痫的发病年龄从10d到28岁不等,30％TSC患者在1岁以内发病,65％在3岁以内发病.12例患者有痉挛发作史.40例患者智力正常,51例患者智力低下.在发病年龄小于1岁的患者中,80％的患者智力低下;在有痉挛发作的患者中,92％的患者智力低下;在有2种发作形式的患者中65％出现智力低下;在每月发作大于4次的患者中有62％出现智力低下;病史5年以上的患者中也有63％的患者出现智力低下. 结论 发病年龄小于1岁、有痉挛发作的患者更容易出现智力低下,应尽早终止发作以提高患者智力.     

Surgical outcome in tuberous sclerosis complex: a multicenter survey

Multicenter, retrospective analysis of 70 subjects with TSC following surgery for relief of epilepsy revealed significant associations between younger age at seizure onset, present/prior history of infantile spasms, interictal focality (bilateral versus unilateral), and absence of residual postoperative predominant tuber, and poorer postoperative outcome (p < 0.01). Ictal multifocality, mental retardation, and discordant EEG and MRI data showed a negative trend toward outcome, but were not significant.     

Infantile spasms in tuberous sclerosis complex: prognostic utility of EEG

Purpose:   To assess cognitive and epilepsy outcomes in tuberous sclerosis complex (TSC) patients with a history of infantile spasms (IS), in relation to spasm history, electroencephalography (EEG) characteristics, genetic mutation, and treatment history.
Methods:   The authors conducted a retrospective review of 45 children and adults with TSC and a history of IS. EEG reports from the time of spasms were evaluated for all patients, and EEG tracings were accessible and evaluated for 20 patients.
Results:   Clinical outcome was unfavorable for the majority of patients. However, 33% had experienced at least one year of seizure freedom at follow-up, and 24% of those tested had IQs above 70. Hypsarrhythmia severity scores varied widely, with some EEGs severely hypsarrhythmic and others essentially normal. Lower IQ was significantly associated with higher hypsarrhythmia severity scores on EEG report, the presence of background disorganization on EEG report, the absence of normal sleep patterns on EEG, and a lower degree of treatment success on vigabatrin. A relationship between poor cognitive outcome and poor epilepsy outcome was confirmed. The correlation between poor epilepsy outcome and a greater degree of background disorganization on EEG approached significance, as did the association between subsequent intractable epilepsy and an older age at IS cessation. A greater than expected ratio of TSC2 to TSC1 patients was observed across this IS population.
Discussion:   Early detection and successful treatment portend a more favorable outcome in TSC patients with IS. Although EEG findings in these patients vary, specific characteristics may serve as clinically useful prognostic markers.     

Arachnoid cysts: diagnosis and treatment

Twenty supratentorial and 10 infratentorial arachnoid cysts are reported. The patients were from 0 to 15 years of age. The commonest presenting symptoms in children were cranial enlargement, epileptic seizures, and psychomotor retardation. Neuroradiological evaluation included CT, metrizamide CT, cisternography, and angiography. Echography was performed in 5 newborns. Therapeutic criteria according to the clinical and neuroradiological findings are reviewed. Cystoperitoneal shunting in combination with ventriculoperitoneal shunting for associated hydrocephalus is considered the treatment of choice.     

Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy

To date, only a few studies have reported that, in tuberous sclerosis, TSC2 mutations are more frequently associated with infantile spasms and cognitive impairment compared to TSC1 mutations. We analyzed the mutational spectrum of patients with tuberous sclerosis in Korea and attempted to explore the associations between genotype and seizure type/outcome. We performed mutational analyses on 70 unrelated patients with clinically confirmed tuberous sclerosis by using direct DNA sequencing and/or multiplex ligation‐dependent probe amplification. The patients’ medical records, including epilepsy type and outcome, were reviewed retrospectively. We identified pathogenic mutations in 55 patients (79%), 25 of which were novel. There were 12 TSC1 mutations and 43 TSC2 mutations. TSC1 mutations included 8 frameshift and 4 nonsense mutations. TSC2 mutations included 12 frameshift, 10 nonsense, 6 splicing, and 6 missense mutations, as well as 4 in‐frame deletions and 5 large deletions. Fifty‐eight patients had epilepsy (83%), including 19 patients with a history of infantile spasms. Compared to patients with TSC1 mutations, individuals with TSC2 mutations had a significantly higher frequency of epilepsy (p<0.05) and tended to have a higher frequency of infantile spasms (37% vs 17%; p<0.3). Most of the patients with TSC2 mutations who developed infantile spasms exhibited subsequent epilepsy (13/14; 93%). However, the presence/absence of infantile spasms did not influence seizure remission or cognitive outcome.     

Evaluation of epileptogenic networks in children with tuberous sclerosis complex using EEG-fMRI

PURPOSE: Ninety percent of patients with tuberous sclerosis complex (TSC) have epilepsy. Identification of epileptogenic areas can be difficult and studies are needed to characterize the epileptogenic network in more detail. METHODS: Five children with TSC and focal epilepsy were studied using simultaneous EEG and functional MRI recordings. Tubers were marked by a neuroradiologist on the anatomical MRI. Spike-associated BOLD (blood oxygenation level-dependent) responses were superimposed with lesions. RESULTS: Thirteen different types of interictal epileptiform discharges (IED) were analyzed with 12 showing a BOLD response, all involving more than one tuber. Five studies had tubers with activations exclusively within the lesion, three studies had lesional activations extending to perilesional areas, and two studies had activations involving exclusively perilesional areas of at least one tuber. Deactivations exclusively within a tuber were found in six studies, lesional deactivations extending to perilesional areas were found in four studies, and tubers with exclusively perilesional deactivations were found in five studies. A BOLD response was found in at least one tuber in the lobe of IED generation and presumed seizure onset (according to telemetry) in all patients. In four patients, the same tubers were involved following different IED localizations. The observed changes were always multifocal, sometimes involving tubers distant from the IED field. DISCUSSION: These findings suggest extended epileptogenic networks in patients with TSC, which exceed networks described in PET and SPECT studies. It was possible to identify specific interictally active tubers. EEG-fMRI provides a noninvasive method to select tubers and areas at their borders for further presurgical investigations.