线粒体脑肌病伴高乳酸血症和卒中样发作

目的报道1例线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)患者的组织学形态、免疫表型、基因型、诊断与鉴别诊断、治疗与预后,总结其临床病理学特征及诊断与鉴别诊断要点。方法与结果女性患者,55岁,临床表现为语言表达障碍伴记忆障碍2月余;头部MRI显示左侧颞叶占位性病变;遂行开颅病变组织活检术。组织学形态观察,片状灰白质结构,散在出血性坏死,部分区域小血管明显增生,管腔扩张、充血,散在淋巴细胞浸润;免疫组织化学染色,淋巴细胞胞膜散在表达CD3和CD20,神经元表达神经元核抗原;高碘酸-雪夫染色呈散在阳性;进一步行肌肉组织活检术,改良Gomori三色染色可见较多散在破碎红纤维,考虑线粒体脑肌病肌肉病理改变。线粒体相关基因检测存在m.3243A G突变(约9%),为致病性突变。最终明确诊断为MELAS。术后予以抗癫、降糖和营养神经治疗。结论 MELAS临床少见,临床表现多样,明确诊断依靠临床表现、组织学形态、免疫表型和基因检测。     

特发性肥厚性硬脑膜炎临床病理分析

目的探讨特发性肥厚性硬脑膜炎(idiopathic hypertrophic pachymeningitis,IHP)的病理诊断要点。方法回顾性分析3例IHP病人的临床和影像学资料,显微镜下观察其组织学形态。男性2例,女性1例,临床表现为头痛、腰背部疼痛伴双下肢麻木、乏力,均行手术切除。结果影像学显示颅内或椎管内硬膜弥漫增厚或呈结节状。组织学:病变内纤维组织显著增生、胶原化,大量淋巴细胞、浆细胞浸润,淋巴滤泡形成,伴有多少不等的中性粒细胞聚集。免疫表型:增生的纤维组织SMA、MSA阳性;浆细胞CD38、CD138、EMA和Ig G阳性,但Ig G4阴性;CD45RO阳性T淋巴细胞明显多于CD20阳性B淋巴细胞。结论 IHP少见,其正确诊断需结合临床和影像学特征以及病理形态综合分析。     

中枢神经系统原发性间变性大细胞淋巴瘤

研究背景中枢神经系统原发性间变性大细胞淋巴瘤可发生于各年龄阶段,通常与免疫缺陷无关,临床及影像学检查易误诊为脑膜炎症性病变,尤其是结核性脑膜炎。而在病理诊断上,形态与中枢神经系统以外的间变性大细胞淋巴瘤相似,间变性淋巴瘤激酶1可呈阳性或阴性。由于易误诊为脑膜炎而于组织活检前应用糖皮质激素治疗,造成组织学观察呈现大片坏死,以及大量组织细胞增生和吞噬现象,故在取材不够全面时易误诊为脑梗死或恶性组织细胞增生性疾病等。本文结合1例12岁中枢神经系统原发性间变性大细胞淋巴瘤患儿的临床资料,通过相关文献回顾,总结该病发病特点和临床表现,以提高临床及病理医师对该病的认识。方法与结果 12岁男性患儿,临床表现为发热、头痛,伴右侧肢体麻木、无力。MRI检查右侧顶叶局部脑回肿胀及软脑膜异常强化,并累及右侧颞叶;左侧顶叶软脑膜异常强化。右侧颞顶叶病变组织活检肿瘤细胞体积较大且形态不规则,胞质丰富、嗜伊红,可见马蹄形和肾形核。免疫组织化学检测肿瘤细胞CD3、CD45RO、CD30、间变性淋巴瘤激酶1和上皮膜抗原表达阳性,CD20和CD79a表达阴性。结论间变性大细胞淋巴瘤是中枢神经系统的罕见病理亚型,临床及影像学极易误诊为脑膜炎症性病变。因此,对临床考虑为脑膜炎,但治疗效果差、病情反复的患者,应尽早进行脑组织活检或反复脑脊液细胞学检查,尤其是脑组织活检为明确诊断之重要手段。     

以肉芽组织和肉芽肿为特征的脑结核病：一例报告并文献复习

目的探讨以肉芽组织和肉芽肿为特征的脑结核病的病理学特征及鉴别诊断。方法回顾分析1例以肉芽组织和肉芽肿为特征的脑结核病患者的临床表现和组织学特征,并复习相关文献。结果男性患者,12岁。临床表现为咳嗽、咳痰、肌肉疼痛和发热。MRI检查显示左侧额颞叶脑膜及顶枕叶、右侧顶叶呈低密度影,左侧小脑半球结节样低密度影。胸部及脊柱CT检查胸骨柄及其体部上段“虫蚀”样骨质破坏,前方软组织肿胀;L2椎体局灶性骨质破坏,椎旁软组织稍肿胀。右侧顶叶立体定向穿刺活检术、胸壁肿物活检术及胸壁窦道切除术后组织形态学观察,右侧顶叶穿刺组织呈边界较清的增生结节,主要由增生的纤维母细胞、泡沫细胞和新生毛细血管组成,伴淋巴细胞、少量浆细胞和中性粒细胞浸润;胸壁肿物、胸骨及软组织则以中性粒细胞浸润为主的化脓性炎性反应为主,伴极少数多核巨细胞浸润。抗酸染色可见右侧顶叶、胸壁及胸骨大量抗酸杆菌生长。结论以肉芽组织和肉芽肿为特征的结核病组织学形态不典型,有时以化脓性炎性改变为主。对于临床表现不典型者,仍应考虑结核病的可能并及时行抗酸染色,以免漏诊和误诊。     

原发性甲状腺功能减退症继发垂体增生伴高泌乳素血症

目的报告1例原发性甲状腺功能减退症继发垂体增生伴高泌乳素血症患者,探讨其组织形态学、免疫组织化学表型、诊断与鉴别诊断、治疗及预后等临床病理学特点。方法与结果女性患者,29岁,临床表现为月经失调1年,溢乳3个月,头痛1周。MRI提示垂体瘤可能性大。遂行经鼻蝶鞍区占位性病变探查术。组织学形态观察,部分腺泡细胞明显增生,呈局灶性结节状。免疫组织化学染色,增生的腺泡细胞弥漫性表达突触素、促甲状腺激素,部分表达催乳素,不表达甲状腺转录因子-1,淋巴细胞散在表达白细胞共同抗原,Ki-67抗原标记指数约1%。病理诊断为垂体增生,最终临床诊断为甲状腺功能减退症。持续服用左甲状腺素钠(优甲乐)100μg/d,随访13个月,一般状况良好。结论垂体增生诊断困难,明确诊断须依靠临床病史、组织学形态特征和免疫组织化学表型,应注意与垂体腺瘤尤其是垂体微腺瘤相鉴别。     

原发性脑膜Rosai-Dorfman 病的临床诊断

目的 探讨颅内Rosai-Dorfman disease(RDD)的临床特点、病理诊断和鉴别诊断.方法 对1 例颅内RDD进行组织形态学和免疫组织化学分析,并复习相关文献.结果 病变以硬膜为基础,与脑实质分界清楚,可见较多组织细胞,淋巴细胞和浆细胞浸润伴纤维化,其中巨大组织细胞胞浆内可见多少不等的淋巴细胞,免疫组化显示,这些组织细胞S-100 蛋白和CD68 标记阳性,散在分布.结论 颅内RDD非常罕见,病理改变为在炎性细胞背景中散在胞浆含多个淋巴细胞的巨大组织细胞,以S-100 阳性,CD68 阳性,CD1a 阴性为特征.     

颅内植物性异物肉芽肿:一例报告并文献复习

目的 颅内植物性异物肉芽肿临床十分罕见,对其临床表现和组织病理学特征进行探讨,避免误诊.方法与结果 报告l例颅内植物性异物肉芽肿患者的临床表现、组织病理学特征和免疫表型,并复习相关文献.男性患者,23岁.主要表现为发作性四肢强直性抽搐,病程7年.头部MRI检查显示,左侧侧脑室前角前下方额叶皮质内长约1.60 cm的小结节状混杂信号影,邻近额叶组织有胶质化表现.术中可见左侧额底病灶与硬脑膜粘连,大小约为3cm×2cm,呈灰褐色,质地较韧,边界不清,部分钙化,血供丰富.光学显微镜观察显示,肉芽肿伴纤维组织增生、透明变性、钙化及淋巴细胞、浆细胞浸润,未见肿瘤细胞及寄生虫病变;病变组织表达波形蛋白和CD68,不表达胶质纤维酸性蛋白、S-100蛋白和上皮膜抗原.结论 颅内植物性异物肉芽肿根据其部位不同临床表现多样,根据异物种类及存留时间的长短,其影像学也存在多样性,但是可以通过组织病理学和免疫组织化学检测明确诊断,与肿瘤、寄生虫病变相鉴别,并初步明确其植被类型.     

IgG4相关特发性肥厚性硬脑膜炎：一例报告并文献复习

目的探讨IgG4相关特发性肥厚性硬脑膜炎的临床表现、影像学及组织病理学特点。方法回顾分析1例IgG4表达阳性的特发性肥厚性硬脑膜炎患者的临床表现、组织学特征,并复习相关文献。结果男性患者,55岁。以癫痫发作起病,主要表现为发作性左侧肢体抽搐。MRI增强扫描显示局部硬脑膜增厚,并呈线样或结节样强化。大体标本观察硬脑膜明显增厚,质地坚硬;光学显微镜下可见硬脑膜异常增厚,纤维结缔组织增生及大量炎性细胞浸润,以淋巴细胞和浆细胞为主,伴少量嗜酸性粒细胞。免疫组织化学染色大量淋巴细胞表达IgG,部分表达IgG4。糖皮质激素和免疫抑制药治疗有效。结论特发性肥厚性硬脑膜炎是一类病因不明的硬脑膜纤维性炎性病变,部分患者可能是IgG4相关硬化性疾病谱中的一员。     

发生于颅眶交界区伴溶骨性改变的B小细胞淋巴瘤/慢性淋巴细胞白血病

目的报告1例具有溶骨性表现、向颅内和眶内侵袭性生长的B小细胞淋巴瘤/慢性淋巴细胞白血病患者,结合文献对其临床表现、影像学特点、组织学形态和免疫组织化学表型、诊断与治疗策略进行分析。方法与结果女性患者,60岁,临床主要表现为左侧眼眶肿胀伴间断性头痛。头部MRI显示,左侧额颞叶、左侧蝶骨大翼、左侧蝶窦外侧壁、左侧眶外侧壁和上壁占位性病变;三维重建CT显示,左侧额骨、颞骨、蝶骨骨质广泛性破坏。于全身麻醉下行肿瘤切除术。组织学形态观察,肿瘤细胞呈弥漫性分布,胞核小而圆、染色质凝集深染、偶见核仁,胞质极少。免疫组织化学染色,肿瘤细胞胞膜CD5呈弥漫性强阳性,CD20、CD43阳性,CD23部分阳性,CD138小灶性阳性,CD38散在阳性,黑色素瘤相关抗原突变型MUM1个别阳性,胞膜和胞质上皮膜抗原阳性,胞质免疫球蛋白κ链阳性;而细胞周期蛋白D1、CD10、CD56、Bcl-6、胶质纤维酸性蛋白、突触素和免疫球蛋白λ链均呈阴性;Ki-67抗原标记指数约70%。最终病理诊断为B小细胞淋巴瘤/慢性淋巴细胞白血病。术后辅以药物化疗。随访6个月仍生存且生活质量满意。结论中枢神经系统淋巴瘤临床表现多样、影像学表现不典型,明确诊断依靠组织病理学检查,B小细胞淋巴瘤/慢性淋巴细胞白血病应注意与中枢神经系统转移瘤、其他原发性中枢神经系统肿瘤和其他血液系统疾病相鉴别,治疗方面于神经导航下大部分切除肿瘤,术后辅以药物化疗和放射治疗可取得较好疗效。     

大脑浅静脉血栓形成伴出血性脑梗死

研究背景大脑浅静脉血栓形成为临床少见脑血管病,病因多样、发病形式和临床表现复杂且不具有特异性,易误诊或漏诊。本文通过对1例大脑浅静脉血栓形成伴出血性脑梗死患者大脑浅静脉解剖学、浅静脉血栓形成病理生理学知识的复习及诊断与治疗要点的回顾,以提高对其诊断与鉴别诊断能力。方法与结果男性患者,18岁。进行性头痛4年伴左侧肢体无力2 d。头部MRI显示右侧额顶叶类圆形占位性病变,MRV显示上矢状窦前2/3显影不清。手术切除右侧额顶叶部分病变组织并去骨瓣减压,术中可见脑组织苍白,部分呈黄色或暗红色,浅静脉怒张;组织学形态观察,软脑膜浅静脉血栓和软脑膜下软化灶形成,大脑皮质多灶性和局部脑实质出血,周围组织大量"格子细胞",并可见"血管套袖"现象,脑实质血管明显增生。术后左手活动明显受限。结论大脑浅静脉血栓形成伴出血性脑梗死临床诊断困难,影像学和血清学检查可提供一定帮助,应重视多学科联合诊断与治疗,以减少误诊和漏诊并积累临床经验。     

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.