原发中枢神经系统淋巴瘤22例临床特点及预后因素分析

目的：探讨原发中枢神经系统淋巴瘤（PCNSL）的临床特点以及预后因素的分析,为临床上对该疾病的诊断和治疗提供依据。方法：总结我院1993年1月至2000年5月诊治的22例PCNSL患者的临床资料,做一回顾性分析,并对各可能预后因素做单因素、多因素回归分析。结果：22例PCNSL中男、女各11例,年龄17－81岁,平均年龄49．5岁。22例中有效随访20例,在随访终点存活9例,死亡11例,存活期1－81个月,中位生存时间14．5个月。并发病是否做过鞘内注射（P＝0．005）及累及部位是局限或弥漫（P＝0．031）是与生存长短相关的两大预后因素。结论：PCNSL发病率仅千万分之一,近年来国外文献报道其发病率有增长势头。手术治疗是PCNSL的主要治疗方法,术后治疗也应当积极,有条件尽量实施鞘内注射,全身化疗是否能进一步提高生存期,有待增加病例数后进一步统计分析。     

原发性中枢神经系统淋巴瘤23例临床分析

目的 探讨原发性中枢神经系统淋巴瘤(PCNSL)的诊断、合理治疗方案和预后的相关因素.方法 收集天津医科大学肿瘤医院2005年1月至2007年12月经病理证实且随访资料完整的23例免疫功能正常的PCNSL患者,其中男10例,女13例,中位年龄50岁.行腰穿检查者18例,检查出瘤细胞者4例.8例行开颅手术切除,15例行立体定向活检术.4例行全颅放疗,6例行以大剂量甲氨蝶呤为基础的联合化疗,13例行放疗联合化疗.分析其治疗、临床特点与预后之间的联系.结果 Kaplan-Meier分析显示本系列患者中位生存期45.0个月,3年生存率56.5％.Log-Rank检验发现放疗联合化疗组(43.8和30.0个月)与化疗组(39.7和29.7个月)的总生存期及肿瘤无进展生存期明显长于单纯放疗组(25.7和19.8个月,P值均＜0.05);放疗联合化疗组的总生存期长于单纯化疗组(P＜0.05),2组间肿瘤无进展生存期无明显差异(P＞0.05).结论 病理诊断仍是确诊的金标准,脑脊液检查发现瘤细胞者也可确诊.以全颅放疗联合化疗为主的综合治疗优于单纯放疗或化疗.     

原发性中枢神经系统淋巴瘤18例临床分析

目的探讨原发性中枢神经系统淋巴瘤(PCNSL)的诊断及治疗措施。方法回顾性分析18例PCNSL的临床、影像学特征及治疗效果。结果18例患者均经手术病理确诊;15例患者行手术治疗和(或)术后放疗和(或)常规CHOP方案化疗,生存期为3~18个月;3例患者手术确诊后使用大剂量甲氨蝶呤(MTX)为主的方案化疗及鞘内注射药物等治疗,生存期均大于36个月。结论PCNSL临床症状及影像学无特征性,诊断困难,易误诊;手术治疗、术后放疗及常规CHOP方案化疗的疗效欠佳,采用易通过血脑屏障药物治疗可取得一定的疗效。     

CNS prophylaxis in lymphoma: who to target and what therapy to use

The purpose of this article is to review the current data on the risk of CNS relapse in patients with lymphoma and the efficacy of CNS directed prophylactic therapy. CNS relapse occurred in 30-50% of those with Burkitt lymphoma and acute lymphoblastic leukaemia/lymphoma prior to the introduction of intensified regimens that include CNS prophylaxis. Most patients with AIDS-related-lymphoma receive a short course of intrathecal prophylaxis but a re-evaluation of type and targeting of CNS prophylaxis is needed. Patients with diffuse large B-cell lymphoma (DLBCL) have a 5% overall risk of CNS relapse but a high risk sub-population can be identified on the basis of raised LDH and >1 extranodal site, testicular or primary breast involvement. CNS prophylaxis for selected patients with DLBCL may be justified by risk but its benefit is not yet proven. Intravenous methotrexate > or = 3 g/m(2) achieves therapeutic levels in CSF and parenchyma and in combination with intrathecal methotrexate would be a reasonable option for prophylaxis.     

Clinical features,prognostic and risk factors of central nervous system infections in patients with systemic lupus erythematosus

The purpose of this study is to describe the etiology, characteristics and outcomes of central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE), while also identifying prognostic and risk factors. Thirty-eight SLE patients with CNS infections were identified from review of all charts of patients with SLE hospitalized from January 1995 to June 2005. These patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non-TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS infections, TB was identified in 19 patients, Listeria monocytogenes in 3 patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient, Gram’s stain positive bacteria in 1 patient, Cryptococcus neoformans in 12 patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome in patients with fungal infection was lower than in patients with TB (P=0.028) and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS infections had a more insidious or atypical clinical presentation. Compared to SLE patients without CNS infections, those with CNS infections were more likely to have low serum albumin levels (P=0.048) and have been receiving higher doses of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of prednisolone within the previous year (P=0.039). In conclusion, low levels of serum albumin and higher doses of received prednisolone are important risk factors for the development of CNS infections in SLE patients. This work was supported by a research grant from Shanghai Leading Academic Discipline Project, Project number: T0203 and a research grant 30371332 from National Natural Science Foundation of China (NSFC).     

系统性红斑狼疮并发中枢神经系统病变的危险因素

目的 探讨系统性红斑狼疮（ＳＬＥ）并发中枢神经系统（ＣＮＳ）病变的危险因素。方法 对４６例并发ＣＮＳ病变的ＳＬＥ患者进行回顾性分析,并与１５２例无ＣＮＳ病变患者做对照。结果 ＳＬＥ的ＣＮＳ表现以癫痫最常见,占５４．３％,其次为精神异常,占３０．４％。与无ＣＮＳ病变的患者对照,两组在发病年龄和病程方面均无显著性差异（Ｐ〉０．０５）。ＳＬＥ病情重者在ＣＮＳ病变组有４３例（９３．５％）,在对照组有４１例     

肝移植术后中枢神经系统并发症的特点及危险因素分析

目的 探讨肝移植术后中枢神经系统并发症(CNSC)的种类、发生率、危险因素及预后.方法 回顾性分析159例原位肝移植(OLT)患者的临床资料,以术后发生CNSC者为Ⅰ组,无CNSC者为Ⅱ组,比较两组各项临床参数.结果 本组OLT术后CNSC发生率为20.1%(32/159).弥漫性脑病占75%(24/32),桥脑中央髓...     

系统性红斑狼疮合并中枢神经系统感染的临床特点分析

目的 分析系统性红斑狼疮(SLE)合并中枢神经系统(CNS)感染的临床特点及相关危险因素.方法 对18例诊断为SLE合并CNS感染的患者和随机抽取的36例SLE患者的临床资料进行回顾性分析.结果 CNS感染组与对照组在大剂量激素冲击(22%与3%,P<0.05),1年内日平均激素用量[(35±18)mg/d与(24±17)mg/d,P<0.05],外周血白细胞[(4.4±3.4)×109/L与(6.7±2.9)×109/L,P<0.05]、淋巴细胞计数[(0.7±0.6)×109/L与(1.5±0.7)×109/L,P<0.01]和临床转归(病死率22%与0,P<0.05)方面的差异有统计学意义.结论 SLE患者合并CNS感染的临床表现不典型.大剂量激素冲击治疗,日平均激素剂量大以及外周血白细胞、淋巴细胞减少是SLE患者发生CNS感染的危险因素.     

Trends in primary central nervous system lymphoma incidence and survival in the U.S.

It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)‐infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992–2011). HIV‐infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV‐infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992–1996) to 12·7% (2007–2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20–39 year‐old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five‐year survival was poor, particularly among HIV‐infected cases (9·0%). Among HIV‐uninfected cases, 5‐year survival increased from 19·1% (1992–1994) to 30·1% (2004–2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV‐infected and HIV‐uninfected PCNSL patients.     

Low-grade primary central nervous system lymphoma in immunocompetent patients

Primary central nervous system lymphomas (PCNSL) are usually diffuse large B-cell non-Hodgkin's lymphomas (NHL). Here we characterize the clinical presentation, course and outcome of patients with low-grade PCNSL. Records of 332 patients screened for inclusion in three multicentre prospective trials were reviewed. Ten patients (3%) with a median age of 59 years and a median Karnofsky performance status of 70% were identified. Seven patients had B-cell and three had T-cell lymphoma. The median growth fraction was 4%. The radiological morphology was unusual for PCNSL in eight patients. Three patients underwent complete tumour resection, combined with chemotherapy in one patient and with chemotherapy plus local radiotherapy in another. Four patients received chemotherapy and three received chemotherapy plus whole-brain irradiation, resulting in four complete remissions, two no-change situations and one progressive disease. Patients had an overall survival (OAS) of 2-58+ months with a 2-year OAS of 67%. Low-grade PCNSL may differ from classical high-grade PCNSL in its clinical features and radiological morphology. The clinical course may be variable and frequently more indolent than in classical PCNSL.     

造血干细胞移植后中枢神经系统并发症的临床研究

目的 探讨造血干细胞移植(HSCT)后中枢神经系统(CNS)并发症的发生率影响因素及预后,提高CNS并发症的诊断和治疗水平,从而改善此类患者的生存.方法 研究对象为自2001年5月至2007年12月在北京市道培医院行HSCT的640例患者,对其中发生CNS并发症患者的临床特点进行回顾性分析和研究.结果 640例HSCT患者中共57例发生了CNS并发症,发生率为8.9%.非血缘、单倍型和间胞相合HSCT后CNS并发症的发生率分别为12.0%(10/83),13.5%(39/289)和3.4%(8/237)(P<0.001).预处理为全身照射(TBI)和非TBI方案的发生率分别为19.4%(7/36)和8.3%(50/604)(P=0.047).年龄<14岁组和年龄≥14岁组的发生率分别为15.3%(9/59)和8.3%(48/581)(P=0.072).恶性疾病中的发病率为8.9%(56/627),非恶性疾病中的发病率为7.7%(1/13)(P=1.000).最常见的并发症为原发病复发和颅内感染.患者总体病死率为57.9%(33/57),其中66.7%(22/33)的患者死亡原因为CNS并发症.结论 单倍型和非血缘移植、TBI的预处理方案是移植后发生CNS并发症的高危因素.而年龄和原发病类型对CNS并发症的发病率无显著影响.早期诊断和积极有效地治疗CNS并发症可以降低其相关病死率,改善患者的预后.     

Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK

Central nervous system (CNS) involvement in non-Hodgkin lymphoma (NHL) is a well-recognised complication. There is no consensus regarding indications for prophylaxis or a standard CNS chemoprophylaxis regimen. Current UK practice was evaluated using a questionnaire. A total of 223 questionnaires were sent to clinicians who administered chemotherapy to patients with NHL; 158 (71%) evaluable questionnaires were returned. The overwhelming majority of respondents used prophylaxis in all cases of lymphoblastic lymphoma (97%) and Burkitt lymphoma (96%). Ninety-six per cent of respondents required risk factors to be present before prophylaxis was initiated in cases of diffuse large B-cell lymphoma. The commonest risk factor was site of involvement (paranasal sinus 88%, testicular 85%, orbital cavity 78%, bone marrow 65% and bone 28%). Other risk factors included stage IV, high International Prognostic Index score, >1 extranodal site and raised lactate dehydrogenase levels (34%, 21%, 16% and 10%). A total of 82% did not give prophylaxis in follicular lymphoma and 90% used intrathecal chemotherapy as their preferred method of prophylaxis. The most popular regimen was 12.5 mg methotrexate with each cycle of chemotherapy for six courses. Thirty-nine per cent used systemic chemotherapy for CNS prophylaxis either alone (4%) or as an adjunct to intrathecal prophylaxis (35%). These variations in the indications and methods of prophylaxis indicate that this subject deserves further review.     

31例成人中枢神经系统白血病临床分析

目的：探讨成人非淋巴细胞白血病(ANLL)患者并发中枢神经系统白血病(CNSL)的临床特征。方法：回顾性分析3l例成人CNSL患者的临床资料。结果：3l例成人CNSL患者中，ANLL20例，分别为M2一M5患者。其中3例确诊于发病初期，l7例确诊于巩固期；40岁以下者27例，占87．0％，平均年龄27．48岁，目前死亡15例，失访2例，生存14例。结论：成人ANLL患者并发CNSL发生率高，病情危笃，预后差；临床应重视其预防治疗。     

Risk factors for poor treatment outcome and central nervous system relapse in diffuse large B-cell lymphoma with bone marrow involvement

Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (≥10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels. K.-W. Lee and J. Yi equally contributed to this study.     

甲状腺机能减退对仔鼠中枢神经系统Ⅱ型脱碘酶mRNA表达的影响

目的观察甲状腺激素机能减退(甲减)时仔鼠中枢神经系统Ⅱ型脱碘酶mRNA(D2-mRNA)的表达,研究甲状腺激素对脑发育调控的机制。方法怀孕Wistar雌鼠随机分为甲减组和对照组,从怀孕15d开始甲减组每日经胃灌注1%丙基硫氧嘧啶2.5ml,所生鼠即为甲减仔鼠。对照组每日经胃灌注生理盐水2.5ml。分别于出生时、出生后14、21和45d处死仔鼠,利用荧光定量PCR的方法,分析各组动物大脑皮质、小脑、脑干、海马及脊髓中D2的表达。结果甲减仔鼠大脑、脑干及脊髓中D2mRNA在出生时及出生后14d时表达量高于对照组,在21d和45d时与对照组无显著性差异;在小脑和海马中D2mRNA的表达量在出生时及出生后14、21d时都高于对照组,只有在45d时与对照组接近。结论甲减时仔鼠中枢神经系统D2表达增加,通过调节甲状腺激素水平对其生长发育起着重要作用。     

Immune surveillance and autoantigen recognition in the central nervous system

The central nervous system (CNS) is considered to be a severely disadvantaged site for the elicitation of immune responses. First, there is no specialised lymphatic drainage. Second, both glia and neuronal cells normally do not express appreciable levels of major histocompatibility complex molecules. Third, the vasculature of the CNS is, at least in most places, lined by endothelial cells that have tight junctions and form a barrier (the blood-brain barrier) against most molecules and cells present in the circulation. Fourth, the cells most important in the initiation of immune responses, the leucocyte dendritic cell, are not present. Nevertheless, the existence of inflammatory diseases of this tissue, occurring naturally as in multiple sclerosis or in animals after peripheral immunisation with CNS autoantigens, indicates that the immune system can access and recognise antigens in this site. How this is achieved has become clearer in recent years and primarily seems to involve extravasation of activated but not resting T cells across the blood-brain barrier, and recognition of antigen on macrophage-like perivascular cells, rather than cells within the CNS parenchyme such as astrocytes or microglia. The processes involved in immunological patrolling of the CNS and development of autoimmune inflammatory disease are reviewed.     

Similar chemokine receptor profiles in lymphomas with central nervous system involvement – possible biomarkers for patient selection for central nervous system prophylaxis,a retrospective study

Central nervous system (CNS) relapse occurs in around 5% of diffuse large B‐cell lymphoma (DLBCL) cases. No biomarkers to identify high‐risk patients have been discovered. We evaluated the expression of lymphocyte‐guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi‐square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL.     

Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas

Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.     

高血压对主动脉夹层患者术后早期中枢神经系统功能的影响

目的分析高血压对主动脉夹层患者术后早期中枢神经系统功能的影响。方法选取南京鼓楼医院2008-11-2011-05主动脉夹层术后患者(n=77),根据是否有中枢神经系统损伤分为损伤组(n=35)和对照组(n=42),应用单因素和多因素Logistic回归分析高血压对主动脉夹层患者术后早期中枢神经系统功能的影响。结果与对照组比较,损伤组高血压患者的比率[80%(28/35)比45%(19/42),P<0.05]、术中失血量[(5037.1±3888.1)比(2466.7±2194.2)mL,P<0.01]升高,术后24h内尿量[(1092.9±727.2)比(1399.3±510.5)mL]、术后回重症加强护理病房(ICU)第一次血气分析pH值[(7.39±0.10)比(7.44±0.08)]、术后回ICU第一次血气分析的动脉血氧分压(PaO2)值[(81.8±30.7)比(116.1±56.9)mmHg,均P<0.05]降低。单因素分析表明高血压史、术中失血量、术后24h内尿量、术后回ICU第一次血气分析的pH值、术后回ICU第一次血气分析的PaO2值可明显影响中枢神经系统功能的恢复;多因素分析表明高血压史(OR0.196)及术后回ICU第一次血气分析PaO2值(OR1.015)是影响中枢神经系统功能恢复的独立危险因素。结论高血压是影响主动脉夹层患者术后早期中枢神经系统功能恢复的独立危险因素。