Objective To analyze the clinical and histology characteristics of a patient with frontal lobe epilepsy diagnosed with mild malformation of cortical development with oligodendroglial hyperplasia, and to recognize the new neuropathological entity. Methods Clinical history, seizure types, neuroimaging, electroencephalography as well as macroscope, histology and immunohistochemistry characteristics were collected from a frontal lobe epilepsy patient and were compared with cases from literature. Results It was a female patient aged 16 years with 12 years history of epilepsy. The seizures manifested as episodes of conscious loss with automatism including grope and voice lasting for seconds. About 10 episodes a day were found and sometimes with secondary generalized tonic-clonic seizures. MRI showed blurring of grey-white matter interface in left orbital frontal cortex. Video-encephalography revealed left frontal lobe origin of seizures. So left prefrontal lobe was removed. Histology showed almost normal cortex neuropil and neurons. Blurring of grey-white interface in some area with patches of proliferation of oligodendrocytes in the corresponding sub-cortical white matter was found. The density of oligodendrocytes was significantly higher in sub-cortical than in deep white matter both shown in HE and Oligo-2 staining. Obvious oligodendrocytes increase and satellite phenomenon in deep cortical layer as well as increased ectopic neurons in sub-cortical white matter were found in the lesion. In proliferation area, there were some nuclei stained with Ki-67, but not as high as tumor. Subsequent follow up for two years proved the operation efficacy and benign prognosis. Conclusions There are special and undiscovered histopathological entities in epilepsy etiology. Although known as grey matter disease, white matter pathology plays an important role in epilepsy pathophysiology which needs further research.

目的 为优化血小板减少的鉴别诊断,论证肾性血小板减少症的存在;方法重新分析血栓性血小板减少性紫癜(TTP)等国内外相关文献病例的客观资料,寻找肾性血小板减少症存在的证据;结果我们发现了疑似肾性血小板减少症6例(高度疑似3例),另外文献计91例尿毒症并发肾性贫血的患者,经我们分析约半数疑似肾性血小板减少;结论 (1)肾性血小板减少症(以肾脏分泌血小板生成素减少为主要原因)理论上推测其存在,实践上有我们揭示的临床病例群支持,应该是存在的;但尚未见我们之外的文献提出.(2)重型狼疮性肾炎并发肾性贫血与肾性血小板减少症的几率可能远高于其并存(而非并发)TTP的几率;(3)北京协和医院报告的两组(14+17)例的系统性红斑狼疮并存“TTP”文献及国外同类文献的诊断难以成立.

PURPOSE:Type IIB focal cortical dysplasia (FCD) is an important cause of drug-resistant epilepsy. However, balloon cells located in the medial temporal lobe have been seldom reported. We aimed to discuss the clinical and pathological features of Type IIB FCD with balloon cells in the medial temporal lobe (MTLE-FCDIIB) and the differential diagnosis with other types of mesial temporal lobe epilepsy.METHODS:Three MTLE-FCDIIB cases were enrolled from Peking Union Medical College Hospital. Clinical and neuroimaging data were analyzed and histology features observed on hematoxylin-eosin (H&E) staining and immunochemical staining, including vimentin, nestin, S-100, CD34, neuronal nuclei antigen (Neun), glial fibrillary acidic protein (GFAP), neurofilament heavy chain (SMI32), were discussed.RESULTS:All cases involved drug-resistant epilepsy patients with childhood onset. The semiology of the epileptic seizure was a highly frequent partial seizure with or without generalized tonic-clonic seizures. Magnetic resonance imaging showed hyper-intensity in the medial temporal lobe without atrophy, different from mesial temporal sclerosis. Histological examination indicated the presence of balloon cells in the white matter of the para-hippocampal gyrus, subiculum, and cornu ammonis with cortical disorganization, and SMI32 positive dysmorphic neurons in the gray matter. Balloon cells were immunohistochemically stained with vimentin and nestin. Granular cell dispersion and pyramidal cell loss were not found.CONCLUSIONS:The presence of balloon cells in the medial temporal lobe is observed in a rare subgroup of FCD, named MTLE-FCDIIB. It has distinct clinical manifestations, neuroimaging features, pathological changes, and prognosis, which should be differentiated from mesial temporal lobe sclerosis and mesial temporal lobe tumors. Our findings enable more accurate diagnosis of mesial temporal lobe epilepsy.

The National Institute on Aging-Alzheimer's Association (NIA-AA) research framework of biological definition of Alzheimer's disease 2018 is introduced to Chinese counterparts to share a common "language" with dementia researchers.The abnormal definitions of Alzheimer's disease (AD),βamyloid deposition (Aβ) and tau,were proposed to be detected by biological methods,and a series of changes before dementia and dementia were proposed to be studied under a unified biological framework.The characteristic biomarkers were defined as AT(N):A is [β amyloid deposition,T is pathological tau protein,and (N) is neurodegeneration.The diversity of the pathological nature of dementia was emphasized,and AD combined with dementia was proposed not to be directly attributable to dementia due to AD.The definition of biomarkers requires more standardization and confirmation of autopsy pathology.

Neurosyphilis occurs in the late stage of systemic syphilis infection; early diagnosis and treatment are crucial to the prognosis. We review 3 autopsy cases with different subtypes of neurosyphilis, that is cases with meningovascular, general paresis, and a combination of the 2, respectively. We investigated the gross morphology and leptomeninges, vessels, cerebral cortex, white matter, brainstem, cerebellum, olfactory bulb and spinal cord microscopically. We found that meningovascular inflammation exists in both early and late phases of neurosyphilis, not only in the meningovascular subtype. Vertebrobasilar artery involvement is common and infarcts of the areas perfused by these arteries in young patient highly suggests neurosyphilis. Damage to the cortical architecture and neuropil is the main mechanism of dementia in general paresis and temporal lobe may not firstly be involved as many other diseases with dementia. Early involvement of olfactory bulbs may help in the early diagnosis of the disease. Our findings indicate that many specific features may help in clinical practice and that further research is needed to clarify the mechanisms.

目的 探讨目前主要的Walker诊断标准和Morava线粒体疾病评分系统对于线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)诊断的优势和局限性、两套诊断标准相互之间的一致性.方法 收集2000年至2013年间我院疑诊MELAS的门诊或住院患者,共67例,归纳总结其临床表现、代谢筛查如血和脑脊液(CSF)的乳酸水平、神经影像、肌肉活检及基因检查等结果,分别按两套诊断标准予以评判,分为确诊、很可能、可能三个不同诊断级别,并予以对照分析.同时对于MELAS诊断中常用的各项检查手段分别予以总结分析,并结合文献探讨其优缺点.结果 按Walker等的诊断标准,67例患者中,36(53.7％)例确诊,9例(13.5％)很可能,22例(32.8％)可能.按Morava等的诊断标准67例患者中确诊36例(53.7％),很可能23例(34.3％),可能8例(11.9％).两套诊断标准比较:判断一致的共35例(52.2％),其中均为确诊的25例,均为很可能的4例,均为可能的6例.判断不一致的32(47.8％)例,其中24例仅相差一个诊断级别,如确诊和很可能之间,很可能和可能之间.结论 全面评价MELAS患者的临床表现、肌肉病理、基因检查、代谢和影像学检查及酶学检测等结果,并坚持个体化的诊断原则才能最大限度的提高诊断的准确性.Morava标准更注重临床,所需检查便于操作,但对于早期患者诊断的阳性率较低.Walker标准涵盖的辅助检查全面,但目前临床上难以全面开展,最终诊断受限.因此,两套标准侧重点不同,应该取长补短.

Objective To characterize the clinical and imaging patterns of adult onset leukodystrophy manifested as spastic paraplegia for early diagnosis and treatment.Methods Clinical and imaging data of 3 patients in Peking Union Medical College Hospital from 2013 to 2014 with adult onset leukodystrophy were reviewed retrospectively.Results Two Krabbe disease and one adrenomyeloneuropathy (AMN) patients all manifested as spastic paraplegia without cognitive impairment.The MRI patterns were bilateral symmetrical long T1 and long T2 signals only affecting cortical spinal tract areas.Subclinical peripheral neuropathy was detected by electrophysiology methods.No adrenal cortical insufficiency was found in AMN patient.On imaging,Krabbe disease mainly affected upper part of cortical spinal tract from motor cortex to internal capsule,and AMN affected lower part from internal capsule to pon and spinal cord.Conclusions Adult onset leukodystrophy can solely manifest as spastic paraplegia.We should take leukodystrophy into differential diagnosis of spastic paraplegia with unknown cause and test enzymes or genes for early diagnosis.

OBJECTIVE:To diagnose muscular dystrophy using Western blot (WB) by improving the method of the protein extraction.METHOD:Firstly,we compared the effect of different sample buffer solutions and processing Methods on the extraction of muscle protein in rats,then selected the appropriate extracting method and the process of the muscular protein.RESULTS:We put the selected sample buffer into the micro-sample,then mixed. The concentration of the extracting protein was much more,and the loss during the process was much less. We extracted enough protein in 62 cases. The protein bands were showed clearly by WB,and the abnormal protein bands were shown in some patients. Compared with the Results of immunohistochemical staining detected the severe abnormal expressions of Dys-R,Dys-C,and Dys-N in the specimens,we did not detect the corresponding target band in WB. We detected the target protein band of the specimens were abnormal position,light or normal staining in WB,while Dys were mildly expressed in immunohistochemical staining.CONCLUSIONS:The improved protein extraction method can save the muscle tissue,and the protein bands can be used for diagnosing the muscular dystrophy. For clinically suspected patients with dystrophinopathy,if normal or mild deficiency is shown by immunohistochemistry,WB should be applied to detect the dystrophin protein band.

>患者女性,28岁,主因"头痛伴恶心、呕吐20 d,左侧肢体无力11 d"于2012年9月收入我院。患者2008年无明显诱因出现皮肤多处色素沉着,于我院皮肤科门诊取皮肤病理示:表皮轻度增厚,局部单核细胞移入,真皮浅层血管周围轻中度淋巴、组织细胞浸润,诊断为"副银屑病","蕈样肉芽肿"不除外,予定期光疗,皮肤病变明显好转。2011年11月开始双侧腹股沟、右侧腋下多发淋巴结肿大,生长速度快,最大约鸡蛋大小,质硬,触之无疼痛,并出现局部皮肤色素沉

Objective To summarize the clinical,laboratory and the muscle histopathology features of patients with Danon disease.Method The clinical documents and laboratory data of 7 patients with Danon disease were analyzed retrospectively.Results Genetic testing was performed in 6 patients and lysosomal-associated membrane protein 2 frame-shift mutations were found.Patients were all male and the age at diagnosis ranged from 13 to 20 years with an average of 16 years.Among the 7 patients,cardiomyopathy was the main clinical manifestation,myopathy was mild or subclinical and mental retardation was common.Besides,2 patients had strabismus.Serum creatine kinase was elevated in all the patients.Echocardiography revealed hypertrophic cardiomyopathy in 5 patients,dilated cardiomyopathy in 1 patient and hypertrophic cardiomyopathy combined with dilated cardiomyopathy in 1 patient.Electrocardiogram revealed pre-excitation syndrome in 5 patients.Electromyogram showed neither myogenic nor neurogenic changes in 2 patients.Autophagic vacuoles in muscle fibers were the character of muscle pathology,and some cytoplasmic vacuoles and granules were positive in dystrophin and spectrin immumohistochemical staining.Endomyocardial biopsy of 3 patients showed extensive vacuoles within some cardiac muscle fibres.Conclusions Danon disease often affects male adolescents,presenting with hypertrophic cardiomyopathy and elevated serum creatine kinase concentration,and myopathy and mental retardation are often mild and can be clinically silent sometimes,which are usually neglected and misdiagnosed as hypertrophic cardiomyopathy.What is more,heart failure is an important predictor of prognosis.Both skeletal and cardiac muscle pathology is characterized by cytoplasmic autophagic vacuoles,even when weakness is not obvious in skeletal muscles.Therefore,skeletal muscle pathology is very important to diagnosis of the disease.

The mutations in the presenilin 2 (PSEN2) gene as causes of early-onset familial Alzheimer's disease (AD) have never been reported in Asia. We conducted a phenotype and pedigree study by performing neuropathological examination and target region sequencing in a family of 3 generations. Six members in this family developed dementia in their fifth decade and died in their sixth decade. The proband was diagnosed clinically with AD, which was confirmed by an autopsy. Target region sequencing showed a novel missense mutation at codon 141 (N141Y) of the PSEN2 gene that predicts an Asparagine-to-Tyrosine substitution in the affected individuals. The result was validated by Sanger sequencing in 7 family members (2 affected and 5 unaffected). The mutation was absent in the 5 clinically unaffected relatives and 188 control subjects. No influence of the APOE genotype was observed. We are the first to demonstrate a novel PSEN2 N141Y mutation in a Chinese Han family with early-onset AD.

神经变性病是神经系统的退行性疾病，病因不明，病程持续进展，且无特效的药物治疗。因此对其病因和机制的研究业已成为国际神经科学领域的研究热点。现有研究认为，缺血缺氧、炎性反应、免疫、血管病理等多种因素可引起微循环障碍，而微循环障碍参与神经元变性过程，甚至先于神经元的变性发生，本文就微循环障碍与神经变性病，特别是阿尔茨海默病和肌萎缩侧索硬化的相关机制进行综述，以期为治疗性研究提供线索。

Objective To investigate the feasibility of multiplex ligation-dependent probe amplification (MLPA) for the molecular diagnosis of mitochondriopathy. Methods Totally 281 patients with suspected mitochondriopathy in Peking Union Medical College Hospital from May 2010 to August 2012 were enrolled in this study. Among them 233 with nervous system damage were from the department of neurology and 48 with suspected Leber hereditary optic neuropathy (LHON) were from the department of ophthalmology. The common mutation sites for mitochondrial disease were detected with MLPA,and the results were verified by mitochondrial DNA (mtDNA) sequencing. Results We found 38 cases carried mtDNA mutations from all 281 cases,and the total detection rate was 13. 5% . Among 48 cases suspected of LHON,19 cases (39. 6%) were found containing 3460G > A,11778G > A or 14484T > C. Among 233 cases suspected of mitochondria related neuropathies,19 cases (8. 2%) were found containing 3243A > G,8344A > G,8993T > G or a large deletion. Except that the large deletion could not be sequenced,the other mutations detected by MLPA were all verified as consistent with gene sequencing results. Conclusions MLPA is a rapid,accurate,and simple method for detecting mtDNA mutation for common mitochondriopathy. It is feasible to be used in clinical diagnostic laboratory.

线粒体脑肌病伴乳酸血症和卒中样发作(mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, MELAS)是一组少见的由线粒体结构和(或)功能异常所导致的以脑和肌肉受累为主的多系统疾病.患者多于10~40岁发病,临床主要表现为运动不耐受、卒中样发作、癫痫、认知功能障碍、高乳酸血症,肌肉活检可见不整红边纤维(ragged red fibers,RRF).

Objective To study the diagnostic value of cerebrospinal fluid(CSF) cytology in the diagnosis of primary central nervous system lymphoma(PCNSL).Methods We retrospectively analyzed the clinical data of 21 PCNSL patients with positive CSF cytological findings.Conventional CSF cytology,immunocytochemistry,flow cytometric immunophenotypic analysis(FCA),and PCR of the rearranged IgH and TCR genes of CSF were performed.Results The clinical and neuroimaging types of 21 patients included meningeal type(n=13),parenchymal type(n=4),ependymal type(n=3),and optic type(n=1).The CSF of all the 21 patients had a number of blast cells or atypical lymphocytes,suspected of lymphoma on conventional cytology.Of the 20 patients undergoing the immunocytochemical studies of the CSF,17 showed B-lymphocyte predominance,which was consistent with the diagnosis of B cell lymphoma.FCA of 7 cases showed a significant increase in the percentage of B cells in 5 patients,indicating B cell lymphoma,and NK/T-lymphocyte predominance in 1 case,indicating an NK/T lymphoma.On analysis of the IgH and TCR genes in the CSF of 4 patients,IgH monoclonal was found in 3 cases and TCR monoclonal in 1 case.Conclusion CSF cytology,immunocytochemistry,FCA,and PCR of the rearranged IgH and TCR genes of CSF are useful in the diagnosis of PCNSL.

OBJECTIVE:To investigate the clinical and pathological characteristics of dermatomyositis with muscular perifascicular atrophy (PFA).METHODS:A series of 104 consecutive patients clinically and pathologically diagnosed as dermatomyositis by muscle biopsy in our laboratory from December, 2003 to August, 2011, were enrolled in this study. Muscle biopsy of all the enrolled patients had shown PFA of muscle fibers.RESULTS:Among the 104 patients, 34 were males and 70 were females with a mean age of 45 years old. Among them, 8 cases had normal electromyogram; 42 had normal serum creatine kinase level; 11 were diagnosed as carcinoma; 75 were found to be combined with interstitial lung disease (ILD). Based on morphologic changes of muscle biopsy, they were divided into pure PFA group with 54 cases and PFA plus focal damage group with 50 cases. Compared with the pure PFA group, there was prominent mononuclear cell infiltration into perimysial intermediate sized vessels and membrane attack complement (MAC) deposition in the intramuscular capillaries in the PFA plus group. Skin biopsy had been taken in 12 cases together with muscle biopsy and had shown the "border effect" of both PFA and interface dermatitis in muscle and skin.CONCLUSIONS:Our study suggests that chronic immune vascular damage and insufficiency in dermatomyositis may cause ischemia and focal myofiber damage in "watershed" regions. The incidence of ILD in our dermatomyositis patients with PFA is high.

Objective In an attempt to clarify the usefulness of combined nerve and muscle biopsy in the diagnosis of neuromuscular disease when compared with traditional sural nerve biopsy.Methods Fifteen biopsies of superficial peroneal nerve (SPN) and peroneus brevis muscle ( PBM ) by one incision performed within one neurological clinic were reviewed.All patients had peripheral neuropathy while 3 of them had myopathy clinically.The diagnostic significance of SPN and PBM biopsies were classified into 3 grade: essential,helpful,no value.Results Of 15 SPN and PBM biopsies,7 showed essential pathological findings which reached the etiological diagnosis, including 5 definite vasculitis, 1 inflammatory demyelinating polyneuropathy and 1 amyloid neuropathy.Five biopsies are helpful for etiological diagnosis,including demyelinating neuropathy,mild inflammation,and microvascular lesion,et al.Three biopsies are of no value for etiological diagnosis which only have nonspecific change such as type 2 fiber atrophy,neurogenic atrophy and axonal degeneration et al. Finally,SPN and PBM biopsies made the definite etiological diagnosis possible in 12 patients.Conclusions SPN and PBM biopsy improved the yield of specific pathological and etiological diagnosis of neuropathy and myopathy such as vasculitis and amyloidosis with minor trauma and side effect.Further clinical and pathological studies will be necessary for a better practice of combined nerve and muscle biopsy.

>病历摘要患者男性,42岁,因"右侧肢体无力45d,加重15d"于2008年11月26日入我院。患者于2008年10月10日突感右侧肢体无力,持物落地。后家人发现其走路时右腿拖曳,反应较前迟钝,但日常生活尚能自理,当地医院予以活血化淤治疗1个月无明显好转。2008年11月11日患者视物成双,次日晨起时突发右侧肢体无力加重,上肢不能抬起,行走费力,但复视症状消失,饮水偶有呛咳,无肢体麻木,无意识