有镶边空泡的远端肌病九例临床和病理研究

目的 探讨有镶边空泡的远端肌病(DMRV)的临床和病理特点。方法 分析我院1990～2001年9例DMRV患者的临床表现和肌活检组织病理特点，其中6例进行透射电镜观察。结果 平均起病年龄25岁，全部患者均为下肢无力起病，远端受累明显，下肢近端、骨盆带肌和上肢肌群也逐渐受累。肌电图示4例为肌源性损害，5例为混合性损害。其病理改变主要为镶边空泡纤维、肌纤维萎缩和肌间质增生，肌纤维坏死相对较轻。电镜观察6例，5例可见大量的髓样结构聚集，4例发现肌质内细丝包涵体，2例有核内包涵体，其中1例可见增大的肌核内染色质完全被细丝取代，核膜破裂，核内细丝包涵体释出进入肌质内。结论 发生在我国的DMRV与日本报道的病例在临床和病理特点上基本一致。电镜观察结果提示胞质内的细丝包涵体来源于崩解的肌核，肌核改变先于肌原纤维的破坏，镶边空泡的形成很可能是肌核崩解的结果。     

杆状体肌病二例并文献复习

目的 探讨杆状体肌病的临床表现和病理特点。方法 分析2例经肌肉活检确诊的杆状体肌病患者的临床和组织病理学特点并复习文献。活检组织常规行HE、MGT、NADH-TR、SDH、NSE、ORO、PAS和ATP染色及超微结构观察。结果 先天性杆状体肌病者属于该病经典型,具有典型的四肢近端无力和肌张力低,伴高足弓畸形;成人起病者可无典型肌病表现。2例患者肌肉病理检查均可见I型纤维占优势,改良Gomori染色可见肌膜下大量蓝紫色粗颗粒样或杆状物质,部分肌纤维萎缩;1例电镜下可见部分肌纤维膜下、肌核旁多个与Z线电子密度一致的杆状小体。结论 成年起病的杆状体肌病临床表现具较大异质性。     

线粒体脑肌病的临床与病理

目的探讨线粒体脑肌病的临床与肌肉病理特点。方法对16例肌活检证实的线粒体脑肌病病例的临床表现、肌肉组织化学及超微结构进行分析。结果16例患者破碎红纤维(RRF)的平均比例为5.9%,11例有中央核增多,13例的SDH/CCO双染示12例有蓝纤维,且与RRF的分布一致。超微结构观察有4例找到典型晶格状包涵体。结论SDH/CCO双染有蓝纤维为线粒体肌病的诊断提供了依据,借此可与其他肌病鉴别。     

三例包涵体肌炎的临床与病理特点

目的探讨包涵体肌炎（ＩＢＭ）的临床与病理特点。方法总结３例ＩＢＭ病人的临床特点，并对肌活检标本进行酶组织化学、组织化学病理和超微病理研究。结果３例女性病人均在２４～３６岁发病，其临床特点为以双下肢无力起病，渐累及上肢，远端肢体受累常见。腱反射消失，血清肌酸激酶正常或轻度增高，肌活检光镜检查发现其主要病理改变为镶边空泡纤维，肌浆或肌核内有嗜酸性包涵体，肌内膜炎性细胞浸润和成群萎缩肌纤维。电镜观察发现３例均有肌浆内细丝或管状细丝包涵体，其中１例有核内包涵体。镶边空泡内含淀粉样细丝、髓样结构、絮状无结构物质和其他胞浆分解产物。肌核改变包括异染色质增多、核变大，核内包涵体及核崩解。结论电镜包埋、半薄切片定位是电镜下寻找包涵体并确诊ＩＢＭ的关键步骤。肌核改变可能是ＩＢＭ的病因基础，镶边空泡和肌浆内包涵体有可能来自于崩解的肌核。     

杆状体肌病12例患者临床与病理特点

目的 探讨杆状体肌病患者临床与病理特点.方法 采用肌肉酶组织化学染色方法和电镜技术观察12例杆状体肌病患者病理特点,收集临床资料进行归纳分析.结果 在本组12例杆状体肌病患者中,7例为先天轻症型,表现为下肢或四肢无力起病,病程进展缓慢,呈良性过程;3例为儿童起病型,均表现为下肢无力,病程持续加重,有肌萎缩现象;2例为成人起病型,双下肢无力起病,累及上肢肌和延髓部肌肉,进展较快,肌萎缩明显,1例出现呼吸困难.部分病例出现狭长面容、双侧弓形足等发育畸形,血清肌酸激酶值正常或稍高,肌电图提示为肌源性损害.在所有患者的肌肉病理切片中,有半数以上肌纤维均出现成堆的杆状体结构;Ⅰ型纤维占优势并呈萎缩现象,且杆状体均出现在Ⅰ型纤维中;改良Gomori染色时杆状体结构最清楚;电镜观察到部分肌原纤维发育不良,如肌丝断裂,排列不整和肌原纤维粗细不一,肌原纤维Z线细小、不规则或消肖失;大量电子密度高的杆状体结构主要出现在肌膜下的肌核周围,少数在肌纤维中央;高倍电镜观察到杆状体结构实际上是肌原纤维中的一段,只是密度很高,但也可是一块无结构的高电子密度体.结论 本组具有3个类型,成人型病情较重,半数以上肌纤维出现杆状体成堆是诊断的关键,电镜有助于确诊.     

眼咽远端型肌病一家系的咽喉功能观察以及骨骼肌病理特点

目的 报道1个眼咽远端型肌病家系的病理和电生理改变特点,分析其吞咽功能障碍的变化规律.方法 先证者为24岁女性,出现进行性加重的眼外肌麻痹、吞咽困难、构音障碍及四肢远端无力和萎缩2年.肌酸激酶轻度升高.家族同代人中还有5例在20～30岁出现类似症状.对先证者进行纤维咽喉镜吞咽功能检查和肌电图检查,对胫前肌进行肌肉病理检查.结果 纤维咽喉镜检查发现软腭上抬差,肌电图检查发现胫前肌呈现肌源性损害伴随肌强直现象.肌肉病理改变特点是肌纤维出现肥大、萎缩、间质纤维化,部分肌纤维内可见镶边空泡,电镜检查显示肌纤维的胞质内存在管丝包涵体.结论 临床和病理检查证实眼咽远端型肌病的存在,软腭运动障碍是出现咽喉症状的主要原因,此病存在肌强直的电生理改变特点.     

少突胶质细胞包涵体对多系统萎缩的诊断意义

目的 观察多系统萎缩脑和脊髓内少突胶质细胞包涵体并评估其诊断意义。方法 应用Gallyas-Braak银染色法研究4例经临床和传统病理方法诊断的多系统萎缩的脑和脊髓标本，以8例运动神经元病的脑和脊髓，6例无神经系统症状和病理改变的同龄人脑标本作对照。结果 4例病例中3例的脑和脊髓白质发现少突胶质细胞包涵体，该包涵体位于少突胶质细胞胞质内，呈半月形、镰刀形、火焰形。主要分布于脑桥、小脑、苍白球－壳核、延髓白质纤维束，脊髓外侧束，且与髓鞘变性脱失的分布一致。另有1例临床缺乏植物神经症状，黑质和脊髓中间外侧柱细胞无明显病变者，其脑和脊髓白质未观察到这种包涵体。所有对照病例的脑和脊髓白质内也未发现少突胶质细胞包涵体。结论 少突胶质细胞包涵体是散发性多系统萎缩特异性较高的病理标志，提示少突胶质细胞变性可能与多系统萎缩的髓鞘脱失有关。     

Nonaka肌病伴面部肌肉受累

目的 报道1个伴随面部肌肉受累及的Nonaka型远端性肌肉病家系的临床和病理特点，讨论其发病机制。方法 先证者在中年早期起病。主要临床表现为胫前肌为主的四肢远端肌无力和肌萎缩，伴随有面肌和胸锁乳突肌力弱以及眼睑下垂，股四头肌不受累。肌酶轻度升高。肌电图提示肌源性损害。对患者进行胫前肌活检，进行组织学，酶组织化学和超微结构检查。家族中其妹妹也具有相同的临床表现。出现下肢远端为主的肌无力和肌萎缩。结果 肌肉病理改变特点是出现肌纤维肥大和萎缩。伴随核内移和肌纤维分裂现象。在部分肌纤维内可见镶边空泡和胞浆体。电镜下可见肌纤维内和核内的管丝包涵体以及髓样小体，其中出现在膜下的管丝包涵体具有细胞核的轮廓，可以看到细胞核变性后形成致密破碎结构。结论 结合患者的家庭史，临床表现和病理学改变特点。此患者可以考虑为Nonaka肌病，我们证实此病可以伴随面部肌肉的受累及。其发病机制可能与肌核的变性有关。     

包涵体肌炎的临床与病理特点(附2例报告)

目的 探讨包涵体肌炎的临床与病理特点。方法 对2例包涵体肌炎患者的临床表现、肌肉组织化学、酶组织化学和超微结构等资料进行分析。结果 本组2例患者分别于41岁及54岁发病,均以双下肢无力起病,远端重于近端,并逐渐向上肢发展;血清肌酶轻～中度升高;肌电图示肌源性损害;肌肉活检光镜下主要表现为肌纤维内出现镶边空泡,少数变性坏死纤维,伴炎性细胞浸润。电镜观察证实肌浆内有大量涡轮状髓样小体及管状细丝包涵体。结论 包涵体肌炎临床表现缺乏特异性,肌肉病理学检查是诊断包涵体肌炎的重要手段。     

线粒体肌病与线粒体脑肌病的酶组织化学和超微结构改变

目的：探讨原发性线粒体肌病与脑肌病的病理特征及临床特点。方法：对11例原发性线粒体肌病与脑肌病患者的临床表现，酶组织化学及超微结构进行分析，结果：11例MGT染色均发现有不整红边纤维（RRF），其中单纯表现为肌无力的患者7例，合并中构神经系统受累者4例，RRF出现比例为6．4％－10．3％，电镜观察11例，9例表现为线粒体数目增多，形态异常，嵴排列紊乱等。均可见线粒体内类结晶状包涵体。2例线粒体改变只见数量增多，未见其他异常。结论：光镜下酶组化染色发现典型RRF，对线粒体肌病与脑肌病的初步论断有重要价值。电镜观察肌膜下线粒体异常增多且形态异常，特别是线粒体内类结晶状包涵体的出现，对本病的确诊有重要意义。     

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.     

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.     

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.