临床孤立综合征

临床孤立综合征（CIS）为多种脱髓鞘疾病的首发表现，有多发性硬化、视神经脊髓炎、横贯性脊髓炎及急性播散性脑脊髓炎等多种转归。早期预测CIS的转归对选择最优化治疗方案极为重要，本文就CIS研究进展进行综述，以提高对该病的认识。     

临床孤立综合征36例临床和磁共振成像特点分析

临床孤立综合征（clinically isolated syndrome，CIS）是指在排除其他疾病的情况下，中枢神经系统脱髓鞘事件的急性或亚急性单次发作，持续时间在24h以上，有多发性硬化、视神经脊髓炎等多种转归。我们收集了36例CIS患者，总结其临床和MRI表现，以增进对此综合征的了解。     

脑脊液细胞因子水平对临床孤立综合征患者复发及转归为多发性硬化的预测价值

目的 探讨临床孤立综合征（CIS）患者急性期脑脊液白细胞介素6（IL-6）等10 种细胞因子 水平对疾病复发和转归为多发性硬化（MS）的预测价值。方法 回顾性连续纳入2015 年1 月至2017 年 8 月在首都医科大学附属北京天坛医院住院的急性期CIS 患者33 例，其中男9 例，女24 例，中位入组年 龄35 岁。使用Luminex 液相芯片法检测脑脊液细胞因子白介素（IL）-6、IL-4、IL-2、IL-10、IL-13、IL-17A、 IL-21、IL-23、干扰素γ（IFN-γ）水平；使用酶联免疫吸附测定法检测转化生长因子β1（TGF-β1）水平。 对患者进行门诊随访，记录其复发、转归为MS 的情况。比较复发及未复发者脑脊液细胞因子的差异。 采用受试者工作特征（ROC）曲线及Cox 回归模型分析脑脊液细胞因子对CIS 患者复发及转归为MS 的预 测价值。结果 入组患者随访时间为10.7～39.9 个月，中位随访时间23.4（17.6，29.1）个月。11 例（33.3%） 患者在随访期出现临床复发，其中4 例诊断为MS。另有2 例患者虽然未出现临床复发，但随访MR 发现 新发病灶最终诊断为MS。复发的CIS 患者首次发病时脑脊液IL-6 水平显著高于未复发的CIS 患者［1.9 （1.4，7.9）ng/L 比1.1（0.9，1.5）ng/L；Z=-2.904，P=0.003］。ROC 曲线分析显示，IL-6 在判断复发时最佳临界 值为1.37 ng/L。单因素Cox 回归结果显示，脑脊液IL-6 ＞ 1.37 ng/L 不能预测CIS 复发（HR=1.54，95%CI： 0.40～5.92，P=0.533）。转归为MS 和未转归为MS 的CIS 患者首次发病急性期脑脊液IL-6 等10 种细胞因 子水差异均无统计学意义（均P＞ 0.05）。结论 本研究所观察的脑脊液IL-6 等10 种细胞因子可能不是 预测CIS 患者复发或转归为MS 的标志物。     

甲状腺抗体与缺血性卒中发生及转归的关系

目的探讨甲状腺抗体与缺血性卒中(CIS)发生、发展及临床转归的关系。方法将382例CIS患者根据甲状腺抗体(TPOAb及TGAb)水平分为正常组、轻度增高组及明显增高组,比较三组患者一般资料及临床病情(NIHSS评分)的差异,并分析甲状腺抗体与CIS病情转归(mRS评分)的关系。结果①与抗甲状腺过氧化物酶抗体(TPOAb)正常组比较,TPOAb轻度增高组与TPOAb明显增高组的大动脉狭窄患者、入院时NIHSS≥8分及卒中1月、3月及1年mRS评分≥8分患者比例明显增高(P0.05);②与抗甲状腺球蛋白抗体(TGAb)正常组比较,TGAb轻度增高组与TGAb明显增高组卒中1月、3月及1年m RS评分≥8分患者比例明显增高(P0.05);③与预后良好组比较,预后不良组入院时、卒中14d NIHSS≥8分患者及TPOAb或TGAb阳性比例更高(P0.01);④CIS患者伴发TPOAb或TGAb阳性,其卒中发生预后不良的风险更高(OR:9.980,95%CI:4.041～24.645,P0.01)或(OR:2.529,95%CI:1.034～6.185,P=0.042)。结论甲状腺抗体TPOAb阳性及其水平可能与CIS合并头颈部大动脉狭窄、卒中后NIHSS评分及临床转归(mRS评分)有关;TPOAb和TGAb阳性可能是CIS患者预后不良的独立危险因素。     

临床孤立综合征转归为视神经脊髓炎的相关因素分析

目的探讨临床孤立综合征(CIS)转归为视神经脊髓炎(NMO)的影响因素。方法收集2004-09-2011-09就诊于作者医院神经内科CIS患者109例。回顾性分析所有患者首次发病时头颅和脊髓MRI特点及临床表现。采用酶联免疫吸附法(ELISA)检测血清水通道蛋白4抗体(AQP4-Ab)水平,另备30份健康者血清作为健康对照组,以高于健康对照组血清AQP4-Ab浓度的均值+3倍标准差者为阳性。结果 (1)随访0.5～7年,中位数为3.0年,四分位数间距为4.6年,转归为NMO 46例,转归为多发性硬化(MS)29例,其余仍是CIS,包括24例脊髓炎,10例视神经炎(ON)。(2)转归为NMO组血清AQP4-Ab水平明显高于MS组、脊髓炎组、ON组和健康对照组(P<0.05)。(3)转归为NMO组AQP4-Ab阳性率为63.03%(29/46),高于转归为MS组的13.79%(4/29)、脊髓炎组的29.17%(7/24)、ON组的20.00%(2/10),差异均有统计学意义(P<0.05)。(4)多因素分析结果提示:AQP4-Ab阳性、NMO颅内典型病灶、脊髓损伤>3个节段、扩展残疾状态量表(EDSS)与CIS转归为NMO有关。结论 AQP4-Ab阳性、NMO颅内典型病灶或者脊髓损伤>3个节段、EDSS评分对预测CIS转归为NMO有临床价值。     

不典型多发性硬化表现为临床孤立综合征53例临床分析

目的 探讨不典型多发性硬化(MS)表现为临床孤立综合征(clinically isolated syndrome, CIS)的临床特点及治疗效果. 方法收集 87 例不典型 MS患者发病的资料,回顾性分析符合 CIS的53 例患者的临床特点、相关检查及治疗,并评估治疗效果. 结果不典型MS患者表现为 CIS占 60.9%,首次发作后经激素冲击治疗可缓解者占 96.2%. 结论 CIS的临床表现多不典型,详细询问病史、体格检查、常规 MRI及诱发电位检查有助于早诊断,早期给予激素冲击治疗可达到有效缓解.     

短时血压变异性与非心源性栓塞性缺血性卒中患者早期转归的相关性分析

目的探讨非心源性栓塞致缺血性卒中(CIS)患者的短时血压变异性与患者临床早期转归的相关性。方法选取于2015年3月-2018年7月延安大学附属医院神经内科住院治疗的非心源性栓塞性CIS患者120例,采集所有患者的一般资料和临床资料,监测所有患者的24h动态血压并计算患者的血压变异性指数,使用改良Rankin量表评价所有患者的近期神经功能转归,根据所有患者的改良Rankin量表评分进行分组,甲组患者98例,乙组患者62例。采用多变量Logistic方法分析患者短时血压变异性和患者临床转归的相关性。结果乙组患者的年龄、高血压发生情况、是否合并感染和急性期服用降压药以及患者的NIHSS评分明显高于甲组患者,差异有统计学意义(t/X~2=-2.014、4.255、30.754、15.190、-10.345,P <0.05)。甲乙两组患者相比,甲组患者收缩压和舒张压的平均值、最大最小值、连续变异性参数和连续变异性参数最大值与乙组患者相比,差异均有统计学意义(P <0.05)。两组患者的昼夜血压节律日间平均动脉压和夜间平均动脉压相比,差异有统计学意义(P <0.05)。平均收缩压、年龄、基线NIHSS评分、患者合并感染和连续变异性参数均为与患者近期转归不良相关的独立危险因素,差异有统计学意义(P <0.05)。结论急性期非心源性CIS患者的短时血压变异性与患者的近期功能转归不良呈明显相关。     

脑脊液中CXCL 13与临床孤立综合征及多发性硬化关系的Meta分析

目的评价脑脊液(CSF)中CXCL 13与临床孤立综合征(CIS)及多发性硬化(MS)的关系。方法计算机检索Pubmed(1966²013)、Embase(19742013)、Embase(1974²013)、Ovid(19932013)、Ovid(1993²013)、Cochrane中心临床对照试验注册数据库(CENTRAL)(2011年第2期)、中国生物医学文献数据库(CBMdisc)(19782013)、Cochrane中心临床对照试验注册数据库(CENTRAL)(2011年第2期)、中国生物医学文献数据库(CBMdisc)(1978²013)、CNKI(19792013)、CNKI(1979²013)、VIP(19892013)、VIP(1989²013)及万方数据库(19782013)及万方数据库(1978²013)等,收集关于CXCL 13与CIS及MS关系的队列研究及病例对照研究。按Cochrane系统评价的方法,由2名研究者独立进行质量评价和资料提取,采用RevMan 5.2软件进行Meta分析。结果共纳入6篇的文献,样本量为1011例,其中病例组(MS及CIS)721例;对照组(神经系统非炎性疾病[NND])290例。与NND及CIS组相比,MS患者CSF中CXCL 13水平高于NND及CIS组(P<0.00001);随访2 y,与未转化的CIS组相比,转化为MS的CIS组CSF中CXCL 13水平高于未转化的CIS组(P=0.009);CSF中CXCL13水平>10 pg/ml的CIS患者,转化为MS的转化率高于<10 pg/ml者(P=0.0001)。结论与NND及CIS组相比,MS的CSF中CXCL 13水平明显升高,对CIS转归为MS有重要的预测价值,提示CSF中CXCL 13的水平与MS的发生发展有关。     

临床孤立综合征转归相关因素分析

目的探讨临床孤立综合征(clinically isolated syndromes,CIS)转归为多发性硬化(multiple sclerosis,MS)和视神脊髓炎(neuromyelitis optica,NMO)的影响因素。方法收集CIS患者106例,据CIS转归结果分为MS组、NMO组和未转归组,以同年龄段健康体检人群100名作为健康对照,分析比较各组之间血清尿酸(uric acid,UA)和同型半胱氨酸(homocysteine,HCY)水平,以多因素回归分析方法分析CIS类型、年龄、性别、病灶数量、影像学特点、扩展的神经功能障碍评分(expanded disability status scale,EDSS)评分、HCY水平、UA水平、治疗是否使用糖皮质激素等因素与CIS转归为MS或NMO的关系。结果总体转归为MS共18例(16.98%),转归为NMO共38例(35.85%)。MS组〔(316.26±186.76)μmol/L〕与NMO组〔(323.95±218.64)μmol/L〕UA水平低于未转归组〔(495.22±259.57)μmol/L〕和健康对照组〔(581.34±283.88)μmol/L〕(P0.05),MS组与NMO组比较,以及未转归组与健康对照组比较差异均无统计学意义(P≥0.05)。MS组HCY水平〔(21.30±12.92)μmol/L〕高于NMO组〔(9.65±4.31)μmol/L〕、未转归组〔(11.40±5.87)μmol/L〕及健康对照组〔(10.86±4.91)μmol/L〕(均P0.05),NMO组、未转归组及健康对照组HCY水平差异无统计学意义(P≥0.05)。多因素回归分析结果提示女性(OR=8.945,P=0.043)、多病灶(OR=6.681,P=0.000)、EDSS评分高于平均值(OR=8.451,P=0.000)与和HCY水平高于平均值(OR=7.839,P=0.000)是CIS易于转归为MS的影响因素,而多病灶(OR=6.947,P=0.000)、UA水平低于平均值(OR=1.368,P=0.024)、初次发作EDSS评分高于平均值(OR=9.002,P=0.000)是CIS易于为NMO的影响因素。结论女性患者、多病灶特点、高HCY水平、EDSS评分高对CIS转归为MS有预测价值;多病灶特点、低血UA水平、EDSS评分高对CIS转归为NMO有预测价值。     

多发性硬化早期表现为临床孤立综合征79例临床分析

目的探讨多发性硬化（MS）早期表现为临床孤立综合征（clinically isolated syndrome，CIS）的临床特点。方法收集96例MS患者发病早期的资料，回顾性分析其中符合CIs的79例患者的临床特点、相关检查、治疗及扩展的功能障碍状况量表评分。结果MS患者早期表现为CIS占82．3％，其中41．1％经MRI检查提示为“多灶性”损害；首次发作后经激素冲击治疗可缓解者占96．1％，其中视神经炎型疗效较显著。结论CIS的临床表现多不典型，详细询问病史、体格检查、常规MRI及诱发电位检查有助于早诊断。早期给予激素冲击治疗可达到有效缓解。     

Clinical re-evaluation of pediatric inflammatory disorders of the central nervous system:a study based on the new classification criteria proposed by the International Pediatric MS Study Group

A retrospective analysis of the clinical and MRI features in 20 Japanese children diagnosed with central nervous system inflammatory demyelinating disorders was performed. Using the new criteria proposed by International Pediatric MS Study Group, half of children were reclassified into clinical isolated demyelinating syndrome (CIS). Presence of seizures and a pattern of diffuse bilateral lesions on brain MRIs are more frequent in children with ADEM than in CIS. However we suggest these features and encephalopathy may be associated with the age of patients. Furthermore, though persistence of abnormal MRI lesions is significantly more likely in the group of CIS, none of these patients had a subsequent recurrence or developed MS during the follow-up period. The prediction of patient prognosis seems to be difficult even based on the new criteria, and the nationwide multicenter analysis may be necessary in Japan for acquiring the definite conclusion.     

Cognitive impairment and structural brain changes in patients with clinically isolated syndrome at high risk for multiple sclerosis

Patients with clinically isolated syndrome (CIS), unlike those with multiple sclerosis (MS), have a selective cognitive impairment which is not consistently related to structural brain changes. Our objective was to characterize a profile of cognitive impairment and its association with structural brain changes in patients with CIS who are at high risk of developing MS. Patients with CIS at high risk for MS on interferon-beta (n = 51) and age-, gender-, and education-matched controls (n = 44) underwent comprehensive neuropsychological testing and MRI brain scan with voxel-based morphometry. The CIS group had lower cognitive performance in verbal and nonverbal memory, information processing speed/attention/working memory, and executive and visuo-spatial functions compared to controls (p ≤ 0.040). Lower cognitive performance was present in 18–37 and 14–26% of patients with CIS at high risk for MS depending on the criteria used. Brain volume was reduced predominantly in fronto-temporal regions and the thalamus in the CIS group (p ≤ 0.019). Cognitive performance was not associated with structural brain changes except for the association between worse visuo-spatial performance and lower white matter volume in the CIS group (β = 0.29; p = 0.042). Our results indicated that patients with CIS at high risk for MS may have a pattern of lower cognitive performance and regional brain atrophy similar to that found in patients with MS. Lower cognitive performance may be present in up to one-third of patients with CIS at high risk for MS, but, unlike patients with MS, variability in their cognitive performance may lead to a lack of consistent associations with structural brain changes.     

Evaluation of the 2005 McDonald MRI criteria for dissemination in space in Afro-Caribbean patients with clinically isolated syndromes

Background:  In 2005, the McDonald MRI criteria for dissemination in space were revised to improve diagnosis of multiple sclerosis (MS) in non-Caucasians.
Methods:  We included patients with a first clinically isolated syndrome (CIS) to assess their performance in the Afro-Caribbean population. Baseline brain and spine MRI examinations were available within 3 months after onset of CIS. The development of a second clinical event was used as the main outcome indicating clinically definite MS.
Results:  A total of 66 patients (52F/14M) were included between January 1998 and January 2008 (mean age: 34.7; median follow-up: 34 months). CIS was classified as spinal cord (30.3%), optic neuritis (28.8%), brainstem (24.2%), multiregional (10.6%), hemispheric (4.5%), or undetermined (1.5%). Overall conversion rate was 42.4% (median: 11 months). The McDonald criteria revised for dissemination in space were fulfilled in 33.3% (sensitivity: 0.39 (±0.18); specificity: 0.66 (±0.15), positive predictive value: 0.46 (±0.20), negative predictive value: 0.60 (±0.15).
Conclusion:  The Afro-Caribbean population is characterized by a strong proportion of CIS in the spinal cord and a lower burden of disease on the baseline brain MRI. This may explain the low sensitivity of the 2005 McDonald criteria for dissemination in space. Further prospective studies emphasizing MRI spinal cord features are needed to improve diagnostic criteria in a population of African descent.     

Clinically isolated syndromes

Clinically isolated syndrome (CIS) is a term that describes a first clinical episode with features suggestive of multiple sclerosis (MS). It usually occurs in young adults and affects optic nerves, the brainstem, or the spinal cord. Although patients usually recover from their presenting episode, CIS is often the first manifestation of MS. The most notable risk factors for MS are clinically silent MRI lesions and CSF oligoclonal bands; weak or uncertain risk factors include vitamin D deficiency, Epstein-Barr virus infection, smoking, HLA genes, and miscellaneous immunological abnormalities. Diagnostic investigations including MRI aim to exclude alternative causes and to define the risk for MS. MRI findings incorporated into diagnostic criteria in the past decade enable MS to be diagnosed at or soon after CIS presentation. The course of MS after CIS is variable: after 15-20 years, a third of patients have a benign course with minimal or no disability and a half will have developed secondary progressive MS with increasing disability. Prediction of the long-term course at disease onset is unreliable. Disease-modifying treatments delay the development from CIS to MS. Their use in CIS is limited by uncertain long-term clinical prognosis and treatment benefits and adverse effects, although they have the potential to prevent or delay future tissue damage, including demyelination and axonal loss. Targets for future therapeutic progress are to achieve safe and effective long-term immunomodulation with neuroprotection and repair.     

转甲蛋白Glu54Lys突变所致家族性淀粉样多发性神经病1例

目的：探讨转甲蛋白Glu54Lys突变引起的家族性淀粉样多发性神经病（FAP）的临床表现和神经病理特点.方法：分析1例Glu54Lys突变所致的FAP患者的临床及腓肠神经病理特点,并与文献所报道的5例病例进行比较分析.结果：转甲蛋白Glu54Lys突变引起的FAP患者起病年龄为26－33岁,病程3－4年进展,临床表现为多发性感觉运动周围神经病,尤以自主神经症状为突出表现.患者同时可伴有玻璃体混浊和心肌肥厚.结论：转甲蛋白Glu54Lys突变引起的FAP起病早,临床症状严重,预后较差.组织病理和基因检测有助于FAP的诊断.     

Clinical isolated syndrome: a 3-year follow-up study in China

Objective

To summarize the characteristics of Chinese clinically isolated syndrome (CIS) patients and their 3-year follow-up results. Investigate the relationship between CIS features and clinical outcomes.

Methods

Forty-nine CIS patients were recruited and 42 of them were able to be followed up for a mean of 38 months (range 26-48 months). We recorded baseline features including patient demographics, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCB) and MRI lesions in brain and spinal cord. The incidence of conversion to clinically definite MS (CDMS) or neuromyelitis optica (NMO) after CIS was calculated, and the relationship between baseline features and CDMS was explored. All data were statistically processed with SPSS for Windows Version 11.5.

Results

After a mean follow-up of 38 months, 10/42 patients had converted to CDMS (24%), and one patient had developed definite NMO. The other 31 patients remained in CIS status. A spinal cord syndrome was the initial CIS manifestation in 57% of patients. The conversion rates to MS were 22% (5/23) for patients presenting with a spinal cord syndrome and 27% (3/11) for multi-focal manifestations. The three-year CDMS conversion rates were 70% (7/10) for patients who fulfilled the MRI dissemination in space criteria (2005 revised McDonald) at onset of CIS, while only 9% (3/32) of patients who did not fulfill these criteria converted to CDMS. Females had significantly higher conversion rate than males.

Conclusion

A spinal cord syndrome was the most common initial presentation of our Chinese CIS group. After a mean follow-up of 38 months, the conversion rate to MS was approximately 25%. The 2005 revised McDonald MRI criteria for dissemination in space is a key prognostic factor for conversion to MS in CIS in Chinese patients.     

Clinically isolated syndromes suggestive of multiple sclerosis, part 2: non-conventional MRI, recovery processes, and management

The onset of multiple sclerosis (MS) in 85% of young adults is with a subacute clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Whereas multifocal brain lesions are present on MRI in many patients with a CIS, some patients have additional abnormalities on quantitative MRI in otherwise normal-appearing white and grey matter that suggest an extensive pathological process. Functional outcome for patients with symptomatic CIS lesions is determined by the interplay of inflammation, demyelination, axonal damage, remyelination, and cortical adaptation. Recovery of function may be accelerated by high dose corticosteroids, and although interferon beta delays the development of a second relapse, its long-term effect is unknown. A better understanding of pathological and pathogenetic processes in patients with a CIS will facilitate the development of disease-modifying treatments for patients with MS before they become disabled. Continued clinical and laboratory investigation of patients with a CIS should be encouraged.     

The persistency of high levels of pSTAT3 expression in circulating CD4+ T cells from CIS patients favors the early conversion to clinically defined multiple sclerosis

Not all patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) develop clinically defined MS (CDMS). At first clinical event we observed increased production of IL17, IFNgamma and IL10 by peripheral blood mononuclear cells from patients with CIS that remained high in remission. In CD4+ T cells pSTAT3 expression was higher in patients who subsequently converted to CDMS than in patients who did not and controls. The persistency of high levels of pSTAT3 in circulating CD4+ T cells from CIS patients after the first clinical event may favor the early conversion to CDMS.     

Shared vulnerability between seizures and psychosis in cocaine addiction?

Cocaine-induced seizures (CIS) and cocaine-induced psychosis (CIP) may be complications of acute cocaine intoxication. CIS could result from a kindling process, involving the glutamate NMDA receptor (NMDAR) phosphorylation state, which is enhanced by activation of the dopamine D1 receptor (D1R). CIP is considered to be more specifically associated with the activity of the dopamine D2 receptor (D2R). The authors describe the case of a 21-year-old woman who presented with recurrent CIP during a period of increased cocaine abuse that ended in two consecutive CIS. This case report may illustrate a possible overlap in the mechanisms underlying CIS and CIP, disclosing some subtle interactions occurring between dopaminergic and glutamatergic receptors during cocaine chronic intoxication. Chronic cocaine exposure usually induces the formation of a NMDAR–D2R complex, which seems to be linked to the usual clinical effects of the drug, but also causes complex formation not to occur in both D2R-based CIP and D1R-based CIS. To explain the case of this patient, we propose a pharmacological hypothesis based on a literature review and implying the lack of formation of this complex, which triggers CIP and CIS. On a more practical level, this case report also encourages practitioners to be aware of the possible co-occurrence of CIP and CIS in cocaine abusers, especially with respect to antipsychotic medications that could be administered in such situations.     

Memory failure has different mechanisms in subcortical stroke and Alzheimer's disease

Patients with extensive subcortical cerebrovascular disease may have impaired memory, often despite the absence of medial temporal or diencephalic strokes. In this group, episodic memory failure may arise from frontal lobe dysfunction based on disruption of frontosubcortical loops caused by lacunae. We tested this idea by studying cognitively impaired subcortical stroke (CIS) patients and Alzheimer's disease (AD) patients with [18F]-fluorodeoxyglucose positron emission tomography using a continuous verbal memory task during the period of tracer uptake. Patients were matched on severity of cognitive impairment and overall memory task performance. As hypothesized, we found a double dissociation in the relations between metabolism and memory in these groups, such that memory in CIS (but not in AD) correlates with prefrontal lobe metabolism, whereas in AD (but not in CIS), memory correlates with left hippocampal and temporal lobe metabolism. Analysis of memory subscores showed that CIS patients made more errors on short-delay trials, which is consistent with working memory failure. It seems that different pathogenic mechanisms underlie episodic memory failure in subcortical cerebrovascular disease and AD.