尿酸与多发性硬化

近年来有关研究发现,多发性硬化病人的血清尿酸水平显著低于对照,且可能与疾病的活动性、病程、神经伤残程度及性别有关。尿酸被成功地用于治疗多发性硬化的动物模型,多发性硬化病人口服尿酸前体肌苷可以使临床症状改善,提示对尿酸与多发性硬化的关系研究,有望为进一步探索多发性硬化发病机理及更合理的治疗方案找到新的突破点。     

尿酸与多发性硬化

1　资料和方法1.1　观察组 :54例 (男 2 8例、女 2 6例 )多发性硬化 (ＭＳ)患者均为神经科住院病例 ,年龄 12～ 60岁 ,所有病例均符合Ｐｏｓｅｒ[1] 等提出的ＭＳ诊断标准。1.2　对照组 :( 1)健康对照组 (ＨＣ) ,为体检中心的健康人群共 56例 ,男女各 2 8例 ,年龄 14～ 62岁。     

多发性硬化合并其它自身免疫性疾病

目的 搪塞多发性化硬化（ＭＳ）合并其它自身免疫性疾病的临床特征及可能机理。方法 回顾总结我院近１０年来收治的ＭＳ病人中合并其它自身免疫性疾病患者的临床资料,并结合文献进行讨论。结果 １７４例有９例合并１种其它自身免疫性疾病,其中克隆病、溃疡性结肠炎、原发性血小板减少性紫癜各１例、银屑病、糖尿病（Ｉ型）、类风湿性炎各２例,其它自身免疫性疾病在ＭＳ发病前出现５例,在ＭＳ病程中出现４例,结论ＭＳ中合并其     

多发性硬化的免疫学发病机制

多发性硬化是一种自身免疫性疾病，具发痫机制至今还未阐明，目前认为可能是一些携有先天遗传易感基因的个体有易发生免疫调节功能紊乱的趋势，在后天环境中外因的作用下，诱发对中枢髓鞘成分的异常自身免疫应答而致病。本文综述了近年来的相关文献和科研成果，旨在探讨多发性硬化的免疫学发病机制。     

多发性硬化患者血清尿酸水平变化的研究

目的　探讨多发性硬化 (MS)患者血清尿酸 (UA)水平的变化及其临床意义。方法　采用酶定量分析法对 4 3例MS患者和 4 5名正常对照者的血清UA水平进行检测。结果　MS组血清UA水平明显低于对照组 (P <0 0 1)。MS组中病程越长 (P <0 0 1)、神经伤残程度越重 (DSS评分越高 ) (P <0 0 5 ) ,血清UA水平越低 ;女性患者UA水平明显低于男性患者 (P <0 0 0 1) ;经过糖皮质激素治疗后血清UA水平明显回升 (P <0 0 0 1) ,但治疗前血清UA水平越低则疗效越差 (P <0 0 1、P <0 0 5 )。结论　MS患者血清UA水平降低 ,且与MS的病程、伤残程度、疗效及性别密切相关。UA水平升高可能为激素治疗MS的一个作用机制     

多发性硬化和尿酸水平的病例对照研究

北美和欧洲国家相继有试验报道尿酸可能对多发性硬化 (multiplesclerosis,MS)有预防、治疗作用[1,2 ] ,但尚未见有关亚洲人种的报道。本研究的目的是通过回顾性病例分析研究探讨中国人中MS和尿酸水平的关系 ,试图为MS患者的诊断、预防、治疗找到新的方法和思路。资料和方法 :1997年 10月至 2 0 0 2年 10月间在我院神经内科住院患者 ,其中根据Poser的诊断标准 (临床或实验室证据支持 )确诊的MS患者 6 5例 ,其中男性 2 6例 ,女性 39例 ,平均年龄 (37± 14 )岁。另选择同期其他不影响尿酸水平的神经内科疾病患者 6 9例为病例对照组 ,其中男…     

尿酸与多发性硬化发生和复发的关系

目的 分析多发性硬化(multiple sclerosis,MS)患者血清尿酸水平的变化,探讨尿酸在MS发生和复发中的作用.方法 收集95例确诊的MS患者的临床、影像学、治疗和血生化检查的资料,同时收集性别、年龄匹配的97名健康查体者的血生化检查结果,分析血尿酸水平与MS的关系.结果 (1)MS患者血尿酸水平较对照组明显降低 (195.6±65.0)μmol/L vs.(256.1±48.0)μmol/L,P＜0.01];按性别分层分析,女性患者血尿酸水平较对照组显著降低 (179.8±53.7)μmol/L vs.(253.2±48.3)μmol/L,P＜0.01),男性患者血尿酸水平与对照组比较无统计学变化.(2)女性MS患者活动期[(171.1±52.4)μmol/L]和缓解期[(207.4±49.7)μmol/L]的血尿酸水平均明显低于正常对照组(均P＜0.01),且活动期MS血尿酸水平较缓解期进一步降低(P＜0.05).(3)血尿酸水平与发病年龄、病程和EDSS评分无相关性.结论 血尿酸水平降低可能与MS的发生和复发有关,其机制可能是血尿酸水平的降低削弱了患者对氧化应激的承受能力.     

血清尿酸与多发性硬化关系的研究

目的 探讨多发性硬化（MS）患者血清尿酸水平的改变与临床的关系。方法 检测88例MS患者（MS组）血清尿酸水平,分析其与临床分期、病程、病情的关系;并与其他神经系统炎症性疾病患者（OIND组）和健康体检人员（正常对照绀）比较。结果 MS组血清尿酸水平明显低于OIND组及正常对照组（均P〈0．05）,处于MS急性复发期患肯的血清尿酸水平低于缓解期患者（P〈0．05）。血清尿酸水平与MS的临床分期独口相关（P〈0．05）,与病橼和扩展后的功能障碍状况量表评分不相关（均P〉0．05）。结论 血清尿酸水平的变化可作为MS诊断及判断MS患者不同临床分期的辅助指标。     

多发性硬化发病机制的研究进展

近年来随着神经免疫学、遗传学、影像学、病毒学方面研究的飞速发展 ,使人们对导致多发性硬化 (ＭＳ)发病和发病后早期损害的机制有了新的认识。现对近期ＭＳ发病机制的研究进展作一综述。1　感染因素ＭＳ在自身免疫过程中选择性地损害少突胶质细胞 ,导致中枢神经系统白质进行性的脱髓鞘。人醇醛基转移酶(ＴＡＬ Ｈ)选择性表达于少突胶质细胞 ,它与脂质的大量产生密切相关 ,是组成髓鞘的基本成分 ,易于遭受氧自由基损害。ＭＳ患者血清和脑脊液中均有ＴＡＬ Ｈ抗体表达。ＭａｒｉａＥｓｐｏｓｉｔｏ等[1] 发现ＴＡＬ Ｈ表位与ＥＢ病毒和Ⅰ型…     

多发性硬化的轴索损伤

多发性硬化（multiple sclerosis，MS）是中枢神经系统常见的慢性炎性脱髓鞘疾病，以往认为该病病理上以脱髓鞘为主，轴索相对保留。MS患者早期或者缓解期临床上是看不到轴索损伤引起的功能缺失的，但当轴索的损伤到达一定阈值，超出中枢神经系统的代偿能力时，就会出现不可逆的神经功能缺失，最终不断累积的轴索损伤可导致MS患者进展性的神经功能缺失。关注轴索损伤对研究脱髓鞘病的病理机制有重要意义，我们将MS轴索损伤相关进展作一综述。     

Serum uric acid and multiple sclerosis

Several studies indicate that patients with multiple sclerosis (MS) have low serum levels of the endogenous antioxidant uric acid (UA), although it has not been established whether UA is primarily deficient or secondarily reduced due to its peroxynitrite scavenging activity. We measured serum urate levels in 124 MS patients and 124 age- and sex-matched controls with other neurological diseases. In addition, we compared UA levels when MS patients were stratified according to disease activity (by means of clinical examination and MRI), duration, disability and course. MS patients had significantly lower serum urate levels than controls (p= 0.001). However, UA levels did not significantly correlate with disease activity, duration, disability or course. Our study favors the view that reduced UA in MS is a primary, constitutive loss of protection against oxidative agents, which deserves further pathogenetic elucidation aimed at future therapeutic strategies. Received: 16 January 2002 / Accepted in revised form: 8 July 2002 This work was partially presented at the 4^th EFNS Congress in Lisbon, Portugal, 7–11 September 1999 and has been published in abstract form in the European Journal of Neurology (Eur J Neurol, 1999, pp. 50–51). Correspondence to S. Sotgiu     

Serum uric acid and multiple sclerosis

Peroxynitrite (PN) has been implicated in multiple sclerosis (MS) and its animal model experimental allergic encephalomyelitis. Uric acid (UA) serum levels of MS patients, a natural scavenger of PN, were found lowered in some recent studies. OBJECTIVE/PURPOSE: The objective of our study was to correlate UA serum levels and several clinical parameters of MS. We also tried to investigate serum UA changes during treatment with immunomodulating or immunosuppressing drugs in the last 6 months. PATIENTS AND METHODS: We measured UA serum levels in 190 patients with MS and 58 age and gender matched patients with inflammatory (IND) and non-inflammatory diseases (NIND) studied as control groups. UA levels were correlated with clinical parameters as type of the disease, duration, disability, magnetic resonance imaging (MRI) activity and female gender. RESULTS: In the overall MS group, patients were found to have significantly lower mean serum uric acid levels compared with the IND (p = 0.0029) and the NIND group (p < 0.0001). UA serum concentrations were not inversely correlated with duration of the disease (p = 0.87), with disability as assessed by Expanded Disability Status Scale (EDSS) score (p = 0.67) and MRI activity (p = 0.36). Treatment with immunomodulating or immunosuppressing drugs had no influence in UA levels (p = 0.85). Patients with Clinically Isolated Syndromes (CIS) were found to have significantly lower UA concentrations compared with IND and NIND patients (p = 0.009 and <0.001, respectively). CONCLUSIONS: Our findings suggest that lower serum UA levels in MS patients may represent a primary, constitutive loss of protection against nitric oxide and the development of CNS inflammation and tissue damage may not have a direct effect to UA serum levels. They also provide support that the earlier increase of UA serum levels might be beneficial in the future treatment of MS.     

Serum uric acid and risk of multiple sclerosis

Because of evidence implicating oxidative stress in multiple sclerosis pathogenesis, it has been postulated that high levels of urate, a potent antioxidant, could reduce risk or favorably influence disease progression. We conducted a prospective study to determine whether serum urate levels contribute to prediction of multiple sclerosis risk. Analyses included 31 cases with blood collected a median of 1.9 years before multiple sclerosis onset from the Nurses’ Health Study and Nurses’ Health Study II cohorts, and 42 cases with collection a median of 14.5 years before onset from the Kaiser Permanente Northern California health plan cohort. Relative risks were estimated by unconditional logistic regression, including 26 controls in the Nurses’ cohorts and 130 controls in the Kaiser cohort. In analyses including only cases in the Nurses’ cohorts where blood was collected shortly before onset, there was a trend toward a lower risk of multiple sclerosis among individuals with higher serum urate, but the association was not significant (multivariable relative risk 0.52, 95% CI 0.22, 1.20, p value 0.13). In contrast, there was no evidence of a decline in risk with increasing serum urate in the Kaiser cohort where there was a longer period of time between blood collection and onset (multivariable relative risk 1.36, 95% CI 0.87, 2.14, p value 0.18). The results of this study suggest that serum urate is not a strong predictor of MS risk. This lack of association is consistent with the interpretation that the lower urate levels among multiple sclerosis cases are a consequence rather than a cause of the disease.     

Serum uric acid level in patients with relapsing-remitting multiple sclerosis

Uric acid (UA) is a hydrophilic antioxidant product associated with multiple sclerosis (MS). We conducted a randomized case-control study to evaluate the serum level of UA in different phases of MS in comparison with levels in a healthy control population. Serum UA was checked in 130 patients with relapsing-remitting MS (85 patients in remitting and 45 patients in relapsing phase) and 50 age-matched controls using a quantitative enzyme-linked immunosorbent assay (ELISA). The mean concentrations of UA in serum was 6.41(±3.18) mg/dL in patients with remitting MS, 4.76(±1.66) mg/dL in patients with relapsing MS and 6.33(±2.94) mg/dL in controls. There was a significant difference between mean UA concentration in relapsing MS and remitting MS (p < 0.001), and between patients with relapsing MS and controls (p = 0.002); however, the difference between levels for patients in the remitting phase of MS and the control group was not significant (p = 0.87). It seems probable that UA has a role in the prevention of disease activity in MS.     

Serum uric acid levels of patients with multiple sclerosis and other neurological diseases

The serum uric acid (UA) levels were measured in 112 patients with multiple sclerosis (MS) and 794 patients with different types of other neurological diseases (OND) or healthy control group. Serum UA levels, along with relevant clinical parameters of MS and OND, were also investigated. MS patients had significantly lower UA levels than those with transient ischemia attack (344.6 +/- 130.6 micromol/L, P = 0.000), cerebral hemorrhage (311.9 +/- 104.7 micromol/L, P = 0.000), cerebral infarction (291.3 +/- 101.6 micromol/L, P = 0.014) and the healthy control group (312.1 +/- 92.8 micromol/L, P = 0.000). MS patients had significantly higher serum UA levels than those with cryptococcus meningitis or meningoencephalitis (178.9 +/- 107.0 micromol/L, P = 0.000) and tuberculous meningitis or meningoencephalitis patients (175.7 +/- 99.9 micromol/L, P = 0.000). There were no significant differences in UA levels between patients with MS and those with facial neuritis, viral meningitis or encephalitis, pulmonary tuberculosis, polymyositis or dermatomyositis, myasthenia gravis, subarachnoid hemorrhage, migraine, Guillain-Barre syndrome and myelitis. In addition, UA levels were independently correlated with gender and duration of MS, but neither with MRI activity, disability nor subtypes of the disease in MS patients. Our data suggest that UA has two biphasic functions: neuroprotective and injurious. Our studies may help physicians to deal with conditions having abnormal UA levels.     

Variation of serum uric acid levels in multiple sclerosis during relapses and immunomodulatory treatment

Uric acid (UA), a product of purine metabolism, may be an antioxidant, perhaps acting as a scavenger of peroxynitrite. Patients with gout have a reduced incidence of multiple sclerosis (MS). A number of studies found that patients with MS have low serum levels of UA, although it has not been established whether this represents a primary deficit or a secondary effect. UA has also been proposed as a marker of disease activity and response to immunosuppressive or immunomodulatory treatment. We retrospectively reviewed 83 relapsing–remitting or secondary progressive MS patients (64 females and 19 males) followed in our Neurology Unit. We collected data concerning demographic variables as age and sex, and clinical variables as age of onset, clinical type, disease duration, EDSS score and total number of relapses. We considered UA levels in three different situations: during a relapse, during remission period and during remission period under immunomodulatory treatment [Interferon Beta 1a im (Avonex; Biogen Idec Inc., Cambridge, MA, USA), Interferon Beta 1a sc (Rebif; Serono Europe Limited, London, UK), Interferon Beta 1b (Betaferon; Bayer Schering Pharma AG, Berlin, Germany) or Glatiramer Acetate (Copaxone; TEVA Neuroscience LLC, Kansas City, MO, USA)]. A Wilcoxon matched pairs test was carried out to determine differences between groups. A P‐value less than 0.05 was considered statistically significant. In 33 patients, we were able to compare at least one UA value obtained during a relapse with at least one when remission without treatment. Mean serum UA levels were significantly lower when measured during a relapse (r: 0.39, P: 0.024). In 27 cases, we compared at least one remission value without treatment with at least one obtained during remission and immunomodulatory treatment. Mean serum UA levels significantly increased when determined during Interferon Beta or Glatiramer Acetate therapy (r: 0.84, P < 0.001). Although we do not know exactly whether and how UA is involved in MS pathogenesis, our data suggest that UA might reflect disease activity or treatment response in MS.