脊髓小脑共济失调3型患者血清神经标志物水平的改变及其临床意义

目的研究脊髓小脑共济失调3型(SCA3)患者血清神经标志物水平的改变及其临床意义。方法用国际协作共济失调评估量表(ICARS)对21例SCA3患者(SCA3组)进行评分。采用放射免疫法检测SCA3组患者和22名正常对照者(正常对照组)的血清神经元特异性烯醇化酶(NSE)、S100B蛋白(S100B)、胰岛素样生长因子1(IGF-1)及其结合蛋白3(IGFBP-3)水平。并对SCA3患者血清神经标志物水平与年龄、发病年龄、病程、CAG重复数、ICARS评分的关系作Spearman相关分析。结果与正常对照组比较,SCA3组血清NSE水平明显升高,血清IGF-1、IGFBP-3水平明显降低(P0.05~0.005)。Spearman相关分析显示,SCA3患者血清NSE水平与病程、ICARS评分呈正相关(r=0.585,r=0.627,均P0.05),血清S100B水平与CAG重复数呈正相关(r=0.619,P0.01),与年龄、ICARS评分呈负相关(r=-0.574,r=-0.539,均P0.05)。结论 SCA3患者的血清NSE、IGF-1、IGFBP-3水平有显著改变,血清NSE和S100B水平与其病程、病情有明显关系。血清神经标志物可反映SCA3患者的病程及病情程度。     

脑卒中患者血清 FFA 水平与胰岛素抵抗的关系

目的：研究脑卒中患者血清游离脂肪酸（FFA ）水平的变化及其与胰岛素抵抗之间的关系。方法选取2012‐03—2013‐03我院收治的脑卒中患者68例为病例组,同时选取同期参加体检的正常人56例为对照组;检测2组血清中游离脂肪酸（FFA）、C反应蛋白（CPR）、空腹胰岛素（fINS）、空腹血糖（fPS）、胰岛素样生长因子1（IGF‐1）的含量,计算胰岛素敏感指数。结果病例组血清中FFA、fINS、fPS的含量明显高于对照组（P＜0.05）,而病例组血清中CPR、IGF‐1的含量明显低于对照组（P＜0.05）,相关分析结果表明,病例组血清中FFA与CPR、IGF‐1呈负相关（P＜0.05）,与fINS、fPS呈正相关。结论脑卒中患者血清中FFA水平明显升高,与CPR和胰岛素抵抗有密切关系。     

小骨窗显微手术治疗高血压脑出血的疗效及对血清 S-100β的影响

目的：观察小骨窗显微手术治疗高血压脑出血的临床疗效及对血清S‐100β蛋白变化的影响。方法将90例出血量30～60 m L的高血压脑出血患者随机分为2组,每组45例,保守组采用内科保守治疗,手术组采用小骨窗显微手术治疗。比较2组不同时间点血清S‐100β蛋白含量、GCS评分及神经功能缺损评分,并于出院后6个月进行GOS预后评估。结果入院时2组血清S‐100β蛋白含量比较差异无统计学意义（ P＞0.05）,手术组入院后1 d、3 d、1周血清S‐100β蛋白含量均低于保守组（P＜0.01）;入院后3 d、1周手术组GCS评分高于保守组（P＜0.01）,相关性分析显示血清S‐100β蛋白含量与GCS评分呈负相关（r＝－1.0369,P＝0.0045）;入院后2周、4周手术组神经功能缺损评分低于保守组（P＜0.01）;出院后6个月,手术组恢复优良率优于保守组（χ2＝4.4643,P＝0.0346）。结论对于出血量30～60 m L的高血压脑出血患者,小骨窗显微手术能够快速清除血肿、降低颅内压,并通过下调血清中S‐100β蛋白含量保护神经细胞,临床疗效优于保守治疗。     

多发性硬化患者血浆溶血磷脂类分子水平及其临床意义

目的：观察多发性硬化（MS）患者血浆中溶血磷脂酸（LPA）和酸性磷脂（AP）以及血清超敏C反应蛋白（Hs‐CRP）水平的变化,探讨这些炎性标志物与MS疾病活动程度的关系。方法选取14例急性期MS患者、15例缓解期MS患者及30名健康体检者,测定其血LPA、AP和 Hs‐CRP的水平变化。结果（1）急性期MS组治疗前血浆 LPA、AP和血清 Hs‐CRP水平均显著高于缓解期 MS组（P＜0.01）和健康对照组（P＜0.01）。（2）急性期MS组经治疗28 d后血浆LPA、AP和血清Hs‐CRP水平显著低于治疗前（P＜0.01）。（3）急性期MS组治疗前血浆LPA与AP水平存在相关性（r＝0.807,P＜0.01）,急性期MS组治疗前血浆LPA和AP与血清Hs‐CRP水平存在相关性（r＝0.574,P＜0.05;r＝0.776,P＜0.01）。结论血浆LPA、AP和血清 Hs‐CRP水平可能作为MS患者疾病活动性的炎性标志物。     

脊髓小脑共济失调3型ICARS评分相关因素分析

目的 探讨国际协作共济失调评估量表(ICARS)评估脊髓小脑共济失调3型患者的相关因素.方法 应用ICARS对29例经基因学检查明确诊断的脊髓小脑共济失调3型家系先证者进行评估,通过统计学方法分析其发病年龄、病程和SCA3/MJD基因胞嘧啶-腺嘌呤-鸟嘌呤(CAG)重复数目与ICARS总评分的相关性.结果 简单线性回归分析结果显示,ICARS总评分与病程呈正相关关系(r=0.576,P=0.004),回归方程为Y=18.992 2.282X2(病程)(F=10.020,P=0.004).多重线性回归分析结果显示,ICARS总评分与发病年龄、病程和CAG重复数目呈正相关关系,回归方程为Y=-110.744 0.97X,(发病年龄) 2.310X2(病程) 1.446X3(CAG重复数目)(F=6.690,P=0.002);3项因素的标准化偏回归系数分别为0.681、0.527和0.575.结论 脊髓小脑共济失调3型患者的ICARS总评分与发病年龄、病程和CAG重复数目呈正相关关系.ICARS为评估共济失调的严重程度提供了可靠的方法.     

遗传性脊髓小脑性共济失调7型的基因突变及临床特征分析

目的 研究遗传性脊髓小脑性共济失调7型（SCA7）的基因突变和临床特征。方法 对临床诊断为脊髓小脑性共济失调（SCA）的15个家系24例患者、20例散发SCA患者、41名家系“正常人”及30名非序列的突变,并利用ABI373例序仪对异常等位基因片段进行DNA测序。结果 24例SCA患者的SCA7等位基因CAG重复数目为9－18。正常人SCA7等位基因CAG重复数目为9－19。检出1例散发患者为SCA7,经基因测序证实,其异常等位基因的CAG重复数目为63。结论 CAG过度扩增是SCA7的致病原因,利用基因突变分析可进行基因诊断,提供症状前诊断及遗传咨询的依据,为基因分型奠定基础。     

脊髓小脑共济失调2型、3型患者10例基因突变与临床表型分析

目的探讨脊髓小脑共济失调（SCA）2型、3型患者的基因突变特点及临床表型。方法总结4个SCAs家系的9例患者和1例散发患者的临床表现，对全部患者、43名家系成员及60名健康对照，采用PCR、荧光PCR、毛细管电泳等技术检测分析SCA2、3基因内CAG三核苷酸重复序列的长度及拷贝数。结果3个家系中的6例患者、1例散发患者存在SCA3／MJD（CAG）n扩展突变，CAG重复数为68—75次；1个家系的3例患者存在SCA2（CAG）n扩展突变，CAG重复数为39—41次。两型患者的临床表现有重叠之处，但在发病年龄、病程进展、神经系统受累部位等方面有明显差异。结论SCA3／MJD型与SCA2型在临床表现上存在一定差异性，有助于鉴别和分型，但基因检测是明确诊断的惟一方法。     

脊髓小脑共济失调12型患者认知功能障碍的研究

目的探讨脊髓小脑共济失调(SCA)12型患者是否存在认知功能障碍及其影响因素。方法采用蒙特利尔认知评估量表(MoCA)、简易精神状态检查量表(MMSE)对5例SCA12型患者(SCA12型组)及13名健康体检者(正常对照组)进行认知功能评估;采用国际协作共济失调评估量表(ICARS)进行共济失调严重程度评分。结果 MoCA评分结果显示,SCA12型组存在认知功能障碍5例(100%),正常对照组存在认知功能障碍10例(77%)。MMSE评分结果显示,SCA12型组存在认知功能障碍2例(40%),正常对照组存在认知功能障碍1例(7.7%)。SCA12型组MoCA和MMSE评分明显低于正常对照组(均P<0.05)。SCA12型组ICARS评分为23～75分,平均(42.6±21.0)分。正常对照组均无共济失调。Spearmans相关性分析显示,SCA12型患者MMSE评分与病程呈负相关(r=-0.894,P=0.041);MoCA抽象功能得分与病程呈负相关(r=-0.884,P=0.047)。结论 SCA12型患者可并发认知功能障碍,这可能与其病程较长有关。     

广东汉族人遗传性脊髓小脑型共济失调基因突变的研究

目的 研究广东汉族人遗传性脊髓小脑型共济失调（SCA）的亚型（SCA1、SCA2、SCA3和SCA7）基因突变分布频率。方法 对临床诊断为SCA的18个家系24例SCA患者、22例散发SCA患者、45名家系“正常人”及30名非家系健康人,通过聚合酶链反应（PCR）及聚丙烯酰胺凝胶电泳（PAGE）等技术检测SCA1、2、3、7基因内CAG三核苷酸重复序列突变,并利用ABI310、377测序仪对异常等位基因片段进行DNA测序。结果 在18个SCA家系中,1个家系（5.55％）有SCA1基因突变,2个家系（11.11％）有SCA2基因突变,7个家系（38.88％）有SCA3基因突变,未发现SCA7突变,。在家系成员中检出1例症状前SCA3患者。22例散发性患者中检出SCA1、SCA2、SCA3和SCA7各1例,各占4.54％。SCA1患者CAG重复数为53～56次,正常人19～34次;SCA2患者CAG重复数为38～45次,正常人20～25次;SCA3患者CAG重复数为74～81次,正常人14～40次。SCA7患者CAG重复数为65次,正常人为9～19次。结论 提示中国人SCA主要为SCA3/MJD型,其次为SCA2和SCA1。基因分析对家族性以及散发性SCA患者的临床确诊和遗传咨询均有重要意义。     

CAG重复长度与脊髓小脑性共济失调3型发病年龄相关性的Meta分析

目的采用Meta分析的方法,探讨CAG重复长度与脊髓小脑性共济失调3型发病年龄的相关性。方法收集关于CAG重复长度与脊髓小脑性共济失调3型发病年龄相关性的文献,采用R软件进行Meta分析。结果本次Meta分析共纳入12篇文献。总样本量为411名。Meta分析结果显示CAG重复长度与脊髓小脑性共济失调3型发病年龄合并相关系数及其95%CI-0. 9952(-1. 10;-0. 90)。亚组分析显示,CAG重复长度与SCA3发病年龄随年份的增加,相关性随之减小。随着样本量的增加,测出的相关系数值降低。种族不同,测出的相关系数有差异。对结果评估分析发现,种族能解释异质性的来源,本次Meta分析不存在发表偏倚。结论 (1)CAG重复长度与SCA3发病年龄存在强烈负相关,即CAG重复长度越长,SCA3发病年龄越小;(2) CAG重复长度占SCA3发病年龄差异的40. 6%,种族差异对SCA3发病年龄存在影响。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.