左旋多巴对老年帕金森病患者血浆同型半胱氨酸水平的影响

目的观察左旋多巴对老年帕金森病(PD)患者血浆同型半胱氨酸(Hcy)、叶酸、维生素B12水平的影响。方法选择55例采用左旋多巴治疗的PD患者为观察组,另选择同时期健康体检者50例为对照组,分别测定观察组治疗前后及对照组的血浆Hcy、叶酸、维生素B12水平。结果观察组治疗后的血浆Hcy、维生素B12水平与治疗前及对照组比较,差异有统计学意义(P0.05);观察组治疗前后与对照组叶酸水平无显著差异(P0.05);回归分析显示,血浆Hcy与叶酸、维生素B12水平呈负相关(P0.05)。结论左旋多巴会提高帕金森病患者体内的血浆Hcy水平,及时补充叶酸、维生素B12利于降低患者体内血浆Hcy水平。     

同型半胱氨酸在帕金森病患者血浆中的变化及临床意义

目的对比研究同型半胱氨酸(homocystein,Hcy)在帕金森病(Parkinson’s disease,PD)和脑梗死患者血浆中的变化,探讨其临床意义。方法检测PD、脑梗死患者及对照组血浆Hcy水平,检测PD、脑梗死患者及对照组血浆叶酸和维生素B_(12)水平。对PD患者血浆Hcy水平与叶酸及维生素B_(12)水平进行相关性分析,对血浆Hcy水平与PD严重程度、病程、临床类型、情绪、认知功能及是否服用美多芭进行相关性分析。结果 (1)PD组、脑梗死组及对照组血浆Hcy水平分别为20±11μmol/L、16±7μmol/L及11±2μmol/L,PD组和脑梗死组血浆Hcy水平均高于对照组,差异有统计学意义(P0.05或0.01),PD组血浆Hcy水平明显高于脑梗死组(P0.01);(2)PD组血浆叶酸和维生素B_(12)水平分别为6±5μg/L和514±345ng/L。PD组血浆叶酸和Hcy水平呈明显负相关(r=-0.453,P0.01);血浆维生素B_(12)和Hcy水平无明显相关性(r=-0.268,P0.05)。(3)按照Hoehn-Yahr分期对PD严重程度进行分组,轻、中、重度PD组血浆Hcy水平分别为16±8μmol/L、21±9μmol/L和35±3μmol/L,三组之间差异有统计学意义(P0.05);(4)血浆Hcy水平与病程、临床类型、情绪、认知功能及是否服用美多芭无关。结论 PD组和脑梗死组血浆Hcy水平明显增高,PD组Hcy水平与疾病严重程度密切相关,PD组血浆叶酸和Hcy水平呈明显负相关。     

血浆同型半胱氨酸水平及N5,N10-亚甲四氢叶酸还原酶基因多态性与老年期抑郁症的关联研究

目的探讨血浆同型半胱氨酸(Hcy)水平及N5,N10-亚甲四氢叶酸还原酶(MTHFR)基因多态性与老年期抑郁症发病的关系.方法采用毛细管电泳-紫外检测法、聚合酶链反应-限制性片段长度多态性技术测定60例老年期抑郁症患者(抑郁症组)和80名正常人(对照组)的血浆总Hcy水平和MTHFR基因多态性.患者入组时评定汉密尔顿抑郁量表(HAMD),治疗第6周末评定疗效(HAMD减分率≥50%为有效,<50%为无效).结果 (1)抑郁症组的血浆Hcy水平[(17±6)μmol/L]明显高于对照组[(12±4)μmol/L],差异有统计学意义(P<0.01).<60岁首次发病(以下简称首发)患者(n=30)的血浆Hcy水平[(16±5)μmol/L]与≥60岁首发患者[n=30,(19±6)μmol/L]的差异无统计学意义(P>0.05);单次发作患者(n=17)的血浆Hcy水平[(18±6)μmol/L]与反复发作患者[n=43,(17±5)μmol/L]的差异无统计学意义(P>0.05);伴心脑血管疾病患者(n=27)的血浆Hcy水平[(19±6)μmol/L]与不伴心脑血管疾病患者[n=33,(16±5)μmol/L]的差异无统计学意义(P>0.05);治疗有效患者(n=40)的血浆Hcy水平[(18±5)μmol/L]与治疗无效患者 [n=20,(17±6)μmol/L]的差异无统计学意义(P>0.05).(2)抑郁症组治疗前后HAMD评分的减分率与血浆Hcy水平无显著相关性(P>0.05).(3)MTHFR C677T基因型有3种,即纯合子突变型(T/T)、杂合子突变型(T/C)和野生型(C/C).抑郁症组的基因型及等位基因频率与对照组比较,差异均无统计学意义(P>0.05).抑郁症组患者的首发年龄、发病次数、是否伴发心脑血管疾病及抗抑郁药治疗第6周末的疗效与MTHFR C677T基因型分布均无关联(P>0.05).(4)不同基因型的受试者(不论是抑郁症组还是对照组)血浆Hcy水平的差异无统计学意义(P>0.05).结论血浆Hcy水平升高可能是老年期抑郁症发病的一个独立危险因素.     

同型半胱氨酸与缺血性脑血管病相关性及控制措施分析

目的探讨同型半胱氨酸(Hcy)与缺血性脑血管病(ICVD)的相关性及控制措施。方法选取ICVD患者85例为ICVD组,选取同期入院体检正常人40例为对照组,检测Hcy水平、叶酸、维生素B12;并观察ICVD患者服用叶酸、维生素B12、维生素B6前后Hcy、叶酸、维生素B12水平变化情况。结果脑梗死组Hcy(17.01±2.96)μmol/L显著高于TIA组、对照组,叶酸为(14.63±7.58)μg/L显著低于TIA、对照组,TIA组、对照组组间差异有统计学意义(P0.05);脑梗死组、TIA组B12水平均低于对照组,但脑梗死组、TIA组间差异无统计学意义(P0.05)。ICVD患者治疗后Hcy水平为(14.64±3.57)μmol/L,显著低于治疗前,叶酸、B12水平分别为(34.05±15.26)μg/L、(724.99±157.67)μmol/L,均显著高于治疗前,差异有统计学意义(P0.05)。结论高Hcy血症与ICVD具有显著相关性,可补充叶酸、B族维生素,降低血浆Hcy水平。     

帕金森病患者伴发高同型半胱氨酸血症的相关因素分析

目的探讨帕金森病(Parkinson’s disease,PD)患者伴发高同型半胱氨酸血症(hyperhomocysteinemia,Hhcy)与左旋多巴(levodopa,L-dopa)治疗的关系。方法收集门诊154例PD患者,检测其同型半胱氨酸(Homocysteine,Hcy)的水平。高于正常值者列为研究组,正常值范围内为对照组,2组就年龄、性别、病程、L-dopa治疗情况、叶酸和维生素B12水平等进行对照分析。结果研究组使用L-dopa治疗者比例(62/76))明显高于对照组(44/78)(P0.01),而其他因素包括性别、年龄、病程、叶酸和维生素B12浓度对Hcy的升高而无明显影响(P0.05);治疗组血浆Hcy浓度(24.34±8.67)umol/L明显高于未治疗组(14.26±6.11)umol/L(P0.01)。结论L-dopa治疗可以导致PD患者的血浆Hcy水平升高,可能是PD患者伴发Hhcy的独立危险因素。     

叶酸和维生素B6、B12联合治疗青年脑卒中合并高同型半胱氨酸血症的疗效观察

目的 观察叶酸和维生素B6、B12联合治疗青年脑卒中合并高同型半胱氨酸(Hcy)血症的疗效.方法 将150例青年脑卒中合并高Hcy血症患者随机分为低剂量叶酸和维生素B6、B12治疗组(低剂量组)、高剂量叶酸和维生素B6、B12治疗组(高剂量组)、对照组,每组50例.用药剂量:低剂量组给予叶酸2.5mg/d、维生素B6 10 mg/d、维生素B12 0.5 mg/d,高剂量组给予叶酸5 mg/d、维生素B6 30 ms/d、维生素B12 1.5mg/d,连续给药4周,对照组不予叶酸和维生素B6、B12治疗.治疗前后检测血浆Hcy浓度,治疗后血浆Hcy浓度＜15 μmol/L为有效;并观察不良反应.结果 治疗4周后低剂量组、高剂量组临床有效率分别是70.4%、71.6%,与对照组(4.6%)相比差异有统计学意义(均P＜0.01);治疗后低剂量组、高剂量组血浆Hcy浓度比治疗前明显降低(下降33.9%和36.1%)(均P＜0.01);对照组治疗后的血浆Hcy浓度无明显下降.3组治疗过程中均未出现不良反应.结论 叶酸和维生素B6、B12联合治疗青年脑卒中合并的高Hcy血症有明显效果,而且高、低两种剂量均有效;无不良反应.     

血浆同型半胱氨酸与脑卒中的关系

目的:探讨血浆同型半胱氨酸(Hcy)与脑卒中的关系。方法:采用微粒子酶免分析(MEIA)测定130例脑卒中患者(急性脑梗死90例、脑出血40例)和80例对照组血浆Hcy浓度,同时测定叶酸、维生素B12、血脂、空腹血糖等,进行Logistic回归分析。结果:卒中组平均血浆Hcy水平[(16.71±6.93)μmol·L-1]明显高于对照组「(10.16±2.71)μmol·L-1](t=8.07,P<0.001);两组中血浆Hcy升高分别有60例(46.15%)和5例(6.25%),差异有显著统计学意义(χ2=36.898,P<0.001)。卒中组平均血浆叶酸水平及维生素B12明显低于对照组;两组血浆Hcy浓度与叶酸及维生素B12水平均呈负相关。Hcy浓度与血压、血糖、血脂、尿酸无明显相关性。Logistic回归分析显示,高Hcy血症的OR值为5.272(95%CI:2.406￣11.552)。结论:高Hcy血症是脑卒中的独立危险因素;Hcy与叶酸、维生素B12呈负相关。     

左旋多巴对老年帕金森病患者认知功能及血浆Hcy、维生素B12、叶酸水平的影响

目的探讨左旋多巴治疗老年帕金森病(PD)对患者认知功能及血浆Hcy、维生素B12及叶酸水平的影响。方法选取老年PD患者70例为观察组,及同期来院体检的老年健康者50例为对照组。观察组患者随机分为低剂量组(n=35)及高剂量组(n=35),观察组予以左旋多巴治疗,连续治疗6个月。采用简易精神状态测量量表(MMSE)和蒙特利尔认知功能评估量表(MoCA)评估患者认知功能,分别于治疗前后对所有患者进行语言及视空间工作记忆测试;检测并比较治疗前对照组及观察组血同型半胱氨酸(Hcy)、维生素B12及叶酸水平变化及治疗前后观察组上述指标的变化。结果治疗前观察组MMSE、MoCA评分及语音性、语义性记忆评分及距离、位置记忆评分低于对照组(P0.05或P0.01);治疗后观察组上述各项评分均较治疗前升高,且治疗后除MMSE、MoCA评分及语言性记忆评分低于对照组外(P0.05或P0.01),其余指标均与对照组无显著差异(P0.05);治疗前观察组血浆Hcy高于对照组(P0.01),而维生素B12、叶酸水平显著低于对照组(P0.05或P0.01);与治疗前比较,治疗后低剂量组及高剂量组血浆Hcy显著升高,而维生素B12水平均降低,且高剂量组与低剂量组间差异显著(P0.01);2组叶酸水平无显著变化(P0.05)。结论左旋多巴可在一定程度上改善老年PD患者的认知功能,但治疗的同时伴有血浆Hcy水平升高及维生素B12、叶酸水平降低,增加不良反应发生,因此临床应加强维生素B12及叶酸等营养支持辅助治疗。     

MTHFR基因多态性及同型半胱氨酸与青年脑血管病的关系

目的:研究Ns,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸(Hcy)水平与青年脑血管病的关系。方法:研究对比40例青年脑血管病患者(首次发病年龄≤50岁)及32例健康青年人的MTHFR基因多态性及血浆Hcy水平。结果:(1)对照组及病例组T/T纯合子率分别为37.5％和22.5％;T等位基因频率分别为60.9％和51.3％,差异均无显著统计意义(均P>0.05)。(2)病例组血浆Hcy几何均值(11.0±2.3μmol/L)显著高于对照组(8.0±1.4μmol/L,P<0.05)。(3)所有受试者中T/T组Hcy值高于C/C组(10.4μmol/L和7.6μmol/L),但差异无显著性(P>0.05)。结合叶酸考虑,进一步将所有受试者按叶酸中位数水平分组。叶酸中位数以下组中,T/T组Hcy值显著高于C/C组(P<0.05);而叶酸中位数以上组中,T/T组Hcy值与C/C组无显著差异。(4)血浆Hcy与叶酸、维生素B12呈显著负相关,与肌酐呈显著正相关。吸烟者血浆Hcy水平显著高于不吸烟者(P<0.05)。结论:(1)本组人群MTHFR基因C677T突变的纯合子在低叶酸状态下可引起血浆Hcy水平显著增高,但与青年脑血管病无显著关系。MTHFR基因677TT纯合突变可能为健康青年人脑血管的保护因素。(2)血浆Hcy水平与青年脑血管病的发生密切相关。(3)叶酸、维生素B12肌酐、吸烟是Hcy的非遗传影响因素。     

抑郁症患者血浆同型半胱氨酸水平的测定

目的:测定抑郁症患者及正常人血浆同型半胱氨酸(Hcy)水平,评价其意义. 方法:收集46例抑郁症(抑郁症组)及38名健康者(对照组)血液标本,采用高效液相色谱法测定血浆Hcy水平,放射免疫法测定血浆维生素B12和叶酸水平,比较两组间差异. 结果:抑郁症组血浆Hcy水平(13.2±6.2)μmol/L,显著高于对照组(7.6±2.4)μmol/L.抑郁症组平均血浆维生素B12水平为(334.0±5.7)ng/L,血浆叶酸水平为(5.9±4.0)μg/L;而对照组分别为(344.0±7.5)ng/L和(7.8±3.0)μg/L,均以抑郁症组显著较低(P<0.05). 结论:血浆Hcy水平升高可能与抑郁症有关.     

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.     

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.     

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.     

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.     

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.