癫痫患者血浆D-二聚体水平变化及其临床意义

目的探讨癫痫患者血浆D-二聚体(D-D)水平变化及其临床意义.方法采用金标方法测定76例癫痫患者(隐源性癫痫组13例,症状性癫痫组63例)和65名正常对照组的血浆D-D含量,并对症状性癫痫组中3组不同发作频率患者的血浆D-D水平进行比较.结果 (1)隐源性癫痫组血浆D-D值与对照组比较无显著差异(P>0.05);(2)症状性癫痫组血浆D-D值显著高于对照组(P<0.01);(3)癫痫非频发(NFE)组血浆D-D值与癫痫频发(FE)组比较无显著差异(P>0.05);(4)癫痫持续状态(SE)组血浆D-D值显著高于NFE和FE组(均P<0.01).结论血浆D-D水平对区别症状性癫痫和隐源性癫痫有一定的临床价值,并可帮助判断癫痫患者的脑损伤程度.     

亚低温持续不同时间对缺血脑组织中氨基酸和单胺类递质含量的影响

目的观察脑缺血后即时亚低温并维持不同时间对脑缺血损伤的影响,探讨亚低温脑保护作用的生物学机制. 方法脑缺血动物模型采用改良的Pulsinelli四动脉阻断法.采用氨基酸分析仪测定脑组织中谷氨酸(Glu)、天门冬氨酸(Asp)、甘氨酸(Gly)和γ-氨基丁酸(GABA)含量;采用荧光分光光度法测定多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA). 结果常温脑缺血组织中Glu、Asp、Gly和GABA的含量明显低于假手术组(P<0.01),亚低温持续30～240 min脑组织中Glu、Asp、Gly和GABA 含量明显高于常温脑缺血组(P<0.05 或P<0.01).常温脑缺血后组织中DA、NE和5-HT的含量明显低于假手术组(P<0.01),5-HIAA含量高于假手术组(P<0.01);亚低温持续30 min脑组织中5-HT含量明显高于常温脑缺血组(P<0.01),5-HIAA的含量低于常温脑缺血组(P<0.05);亚低温持续60～240 min脑组织中DA、NE和5-HT含量明显高于常温脑缺血组(P<0.05或P<0.01),5-HIAA含量低于常温脑缺血组(P<0.01). 结论脑缺血后即时亚低温明显减轻常温脑缺血时组织中氨基酸和单胺类神经递质的代谢紊乱,提示亚低温减轻脑缺血损伤作用最好是在脑缺血后立即实施,并持续达1 h以上效果更明显.     

东菱克栓酶治疗急性缺血性卒中疗效评价

目的探讨东菱克栓酶(东菱迪芙)对急性缺血性卒中患者神经功能缺损评分的改善作用以及对纤维蛋白原和血小板的影响.方法将110例急性脑卒中病人随机分为治疗组80例与对照组30例.治疗组采用东菱迪芙治疗,对照组采用血塞通注射液治疗.两组病人分别在入院时、3周后进行神经功能缺损评分及纤维蛋白原、血小板的评定与检测,并在3月后进行神经功能缺损评分的随访,进行比较.结果东菱迪芙组在3周时(P<0.05)及3月时(P<0.01)神经功能缺损评分改善方面均优于对照组,3月时两组的有效率分别为93.75%和76.67%,治疗组更佳(P<0.01),3周时治疗组在降低纤维蛋白原方面优于对照组(P<0.01),对血小板计数无影响(P>0.05).结论东菱迪芙对急性缺血性卒中患者有确切治疗作用.     

纳洛酮对皮质下动脉硬化性脑病认知功能改变的疗效观察

目的观察皮质下动脉硬化性脑病应用纳洛酮治疗后对改良简易心理状况检查(MMSE)及修订的Barthel指数评分(MBI)的变化。方法将67例皮质下动脉硬化性脑病患者随机分为纳洛酮治疗组和常规药物治疗组，治疗前和治疗2周、5周分别进行MMSE及MBI评分对比。结果两组治疗后MBI评分比治疗前提高，但无显著性差异(P>0．05)。两组治疗2周后MMSE评分对照组无明显提高(P>0．05)，治疗组显著提高(P<0．05)，但与对照组治疗后比较，无显著性差异(P>0．05)；5周后两组与治疗前比较，对照组有显著性差异(P<0．05)，治疗组有非常显著性差异(P<0．01)，且与对照组治疗后比较，亦有显著性差异(P<0．05)。结论应用纳洛酮治疗皮质下动脉硬化性脑病可显著提高MMSE评分，疗效可靠，作用快。     

依达拉奉治疗急性缺血性卒中的临床观察

目的探讨羟自由基清除剂依达拉奉(必存)治疗急性脑梗死患者的临床疗效.方法将60例急性脑卒中病人随机分为治疗组与对照组各30例,两组均用欣易通治疗,治疗组加用必存,对照组加用胞磷胆碱.两组病人分别在入院时、3周后及3月后进行Bathel指数(BI)总分及日常生活活动能力(ADL)积分的评定并进行比较.结果治疗组在3周时(P<0.05)及3月时(P<0.01)BI总分改善方面均优于对照组,3月时两组的有效率分别为86.67%和76.67%,治疗组更佳(P<0.05),在ADL改善方面,治疗组亦明显优于对照组(P<0.05).结论必存对急性缺血性卒中患者有一定疗效.     

丙炔苯丙胺治疗帕金森病多中心、随机、对照开放临床研究

目的观察丙炔苯丙胺治疗帕金森病(PD)的临床有效性和安全性.方法采用多中心、随机、对照开放研究方法,对已使用PD治疗药物但疗效不佳的143例PD患者,分别给予丙炔苯丙胺和维生素E或单独维生素E治疗12周.治疗前后对所有PD患者进行统一帕金森病评分量表(UPDRS-Ⅲ)评分、Hoehn-Yahr分级和Hamilton抑郁量表评分以评估药物疗效,同时观察不良反应.结果丙炔苯丙胺治疗组UPDRS-Ⅲ各项评分,除右上肢动作治疗前后比较无显著性差异外,其他各项均较治疗前显著改善.与对照组比较,治疗组患者静止性震颤、强直、手指拍打、手运动、手部轮替动作等症状的改善差异有显著性意义. 治疗组12周后UPDRS-Ⅲ总分为(19.9±10.7)与对照组(27.6±12.0)比较差异有显著性意义.治疗组12周后总有效率为48.5%,显著高于对照组的8.3%(P<0.01).治疗组Hoehn-Yahr分级减级≥1者25例(39.0%),与对照组(4.0%)相比有显著差异(P<0.01).丙炔苯丙胺对帕金森病患者的部分抑郁症状有明显改善(P<0.01).治疗组副作用的发生率为31.0%,显著高于对照组4.2%(P<0.01),但多数症状轻微,不影响治疗.结论丙炔苯丙胺对PD的主要症状震颤、少动和强直及伴随的抑郁症状有明显疗效,副作用主要为失眠、头晕等主观症状,多数较轻微.     

枸橼酸坦度螺酮改善小脑性共济失调临床研究

目的观察枸橼酸坦度螺酮对改善小脑性共济失调症状的临床疗效。方法选取有小脑性共济失调症状的患者35例口服枸橼酸坦度螺酮治疗,治疗前后分别用共济失调量表及汉密尔顿焦虑量表进行评定。结果治疗后患者姿势和步态障碍、动态功能较治疗前有明显改善(P<0.01),语言障碍和眼球运动障碍较治疗前无明显改善(P>0.05),轻中度患者治疗前后焦虑评分无明显差异,重度患者治疗后焦虑评分明显降低(P<0.01)。结论枸橼酸坦度螺酮短期内可有效改善患者小脑性共济失调症状。     

异丙酚治疗老年脑出血术后患者的疗效观察

目的观察异丙酚治疗老年脑出血术后患者的疗效.方法将48例老年脑出血术后患者随机分为异丙酚组和对照组,各24例.异丙酚组给予异丙酚1～4 mg/kg/h微泵持续输注,同时对症支持治疗.对照组仅对症支持治疗.监测两组患者术后恢复过程中的平均动脉压(MAP)、心率(HR)、颅内压(ICP)及动、静脉血氧含量差(AJDO2),记录术前和术后第7天的临床神经功能缺损程度评分.结果异丙酚组ICP和AJDO2较用药前明显降低(P<0.05),MAP和HR无显著变化;对照组MAP、HR、ICP和AJDO2较异丙酚组明显升高(分别P<0.05和P<0.01).术后第7天异丙酚组的临床神经功能缺损程度评分明显低于对照组(P<0.05).结论异丙酚有助于老年脑出血术后患者的脑保护.     

自杀行为患者血小板5-HT浓度

目的 通过测定伴自杀行为的精神病患者血小板5-HT浓度,以探讨其5-HT功能与自杀行为的关系。方法 研究组65例(男21例,女44例);疾病对照组60例(男25例,女35例)。采用HAMD及PANSS评定证状。在治疗前及治疗后6周检测血小板5-HT浓度,采用HPLC及电化学检测仪测定浓度。结果 治疗前两组血小板5-HT浓度的差异无统计意义,治疗后两组差异有统计学意义(P为0.012)。自杀1次与自杀至少2次者之间治疗前血小板5-HT的差异有统计学意义(P为0.035)。治疗后HAMD及PANSS评分的变化与血小板5-HT浓度变化之间无显著相关性。结论 精神疾病伴自杀行为者血小板5-HT浓度未见显著下降。自杀至少2次者的浓度明显降低,提示与1次自杀者之间存在异质性。精神症状的变化与血小板5-HT浓度的变化之间无显著相关性。     

文拉法辛缓释片对癫痫伴抑郁障碍患者血清DA、5-HT和炎症因子水平影响

目的探讨文拉法辛缓释片治疗对癫痫性抑郁障碍患者血清DA、5-HT和炎症因子水平的影响。方法收集2013年1月~2015年12月期间我院收住的癫痫性抑郁障碍患者92例,按照随机数字表法随机分为观察组46例与对照组46例。在抗癫痫药物治疗的基础上,对照组加用盐酸氟西汀胶囊治疗,观察组加用文拉法辛缓释片治疗,两组疗程均为8周。观察比较两组患者治疗前后血清DA、5-HT和炎症因子水平。结果 (1)治疗前后两组患者的HAMA和HAMD评分差异均无统计学意义(P0.05);且治疗后两组患者的评分均较治疗前明显降低(P0.05);(2)与治疗前相比,治疗后两组患者血清DA和5-HT水平明显升高,IL~(-1)β和IL-4水平明显降低(P0.05);且与对照组相比,治疗后观察组患者的血清5-HT水平明显升高,IL~(-1)β和IL-4水平明显降低(P0.05);(3)两组均未见严重药物不良反应。结论文拉法辛缓释片治疗癫痫性抑郁障碍患者疗效显著,与氟西汀相当,其可能通过升高5HT水平、降低IL~(-1)β和IL-4水平来发挥作用。     

Pharmacological treatments of cerebellar ataxia

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.     

Treatment of cerebellar ataxia with 5-HT1A agonist

Effective, pharmacologic approaches to the treatment of cerebellar ataxia are lacking or inadequate. We recently reported preliminary evidence that tandospirone citrate (tandospirone), a 5-HT1A agonist, improved cerebellar ataxia in patients with Machado-Joseph disease (MJD). In the course of that study, we found that such treatment also alleviated the pain associated with cold sensations in the legs, insomnia, anorexia, and depression, all of which are thought to be mediated through activation of the 5-HT1A receptor. In this paper, we reviewed the few published clinical trials that involved the use of 5-HT1A receptor agonists for the treatment of cerebellar ataxia, and discussed the current theories regarding their mechanism of action. Cortical cerebellar atrophy (CCA) was reported, in a double-blind study, to be amenable to treatment with tandospirone. Other types of spinocerebellar degeneration (SCD) i.e., olivopontocerebellar atrophy (OPCA) and Machado-Joseph disease (MJD) have also been reported to respond to the drug, but these have been small studies. Responsive patients exhibited only mild ataxia. The doses of 5-HT1A agonists that have been used successfully ranged from 12.5 mg/day to 60 mg/day (or 1 mg/kg), and were well tolerated by most patients.     

The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression

Depression is related to the alterations of the central serotonergic system and some antidepressants achieve their therapeutic effects through alteration of serotonin (5-HT) (re)uptake. Peripheral biochemical markers, platelet and serum 5-HT concentrations, platelet monoamine oxidase (MAO) activity, plasma levels of cortisol and prolactin (PRL), were investigated in patients with major depression before and after 4 weeks of treatment with paroxetine (an inhibitor of 5-HT uptake) or tianeptine (a stimulator of 5-HT uptake). Study was open, single center and included female depressed patients, 21 treated with tianeptine (37.5 mg/day) and 15 treated with paroxetine (20 mg/day), and 11 drug-free healthy women (controls). Before treatment, depressed patients as a group had significantly higher serum 5-HT and cortisol concentrations than healthy controls. There were no differences in the other biochemical markers. Response to antidepressant treatment was estimated according to the 50% fall in the initial scores of Hamilton Depression Rating Scale (HAMD) after 4 weeks of treatment. Good therapeutic response was observed in 47% and 45% patients treated with paroxetine and tianeptine, respectively. Paroxetine treatment induced significant decrease in platelet 5-HT concentrations in both responders and nonresponders, while no alterations in platelet 5-HT values were found in tianeptine-treated patients. There was a subgroup of depressed patients in paroxetine-treated group with high pretreatment platelet 5-HT concentration and later poor therapeutic response to paroxetine treatment. Serum 5-HT values, platelet MAO activity or plasma cortisol or PRL levels were unchanged after both treatments. The results suggest that pretreatment platelet 5-HT levels, but not other peripheral biochemical markers, might predict therapeutic outcome at least in paroxetine-treated patients.     

四磨汤口服液联合西酞普兰治疗伴焦虑抑郁的腹泻型肠易激综合征患者的疗效观察

目的 探讨四磨汤口服液联合西酞普兰治疗伴焦虑抑郁的腹泻型肠易激综合征(IBS)患者的临床疗效及对血清5-羟色胺(5-HT)、去甲肾上腺素(NE)、髓过氧化物酶(MPO)的影响.方法 选取我院2017年1月～2019年6月期间收治的118例伴焦虑抑郁的腹泻型IBS患者作为研究对象,采用随机数字表分为对照组和观察组,每组各...     

Relationship between parameters of serotonin transport and antidepressant plasma levels or therapeutic response in depressive patients treated with paroxetine and amitriptyline.

In a double-blind clinical study, antidepressant plasma levels, parameters of platelet serotonin (5-HT) transport (Km, Vmax and basal platelet 5-HT content) and therapeutic response were measured in depressive patients treated with either paroxetine (30 mg/day) or amitriptyline (150 mg/day) for 6 weeks. No correlation could be found between paroxetine plasma levels and therapeutic outcome after 2, 4 and 6 weeks of treatment. In contrast to the amitriptyline group, a marked increase in Km from baseline to week 2 was determined in paroxetine-treated patients, with Km increase being correlated with paroxetine plasma levels at week 2. However, no significant relationship could be found between 5-HT transport parameters and any of the outcome measures in either treatment group.     

Double-blind crossover study with dolasetron mesilate,a 5-HT<Subscript>3</Subscript> receptor antagonist in cerebellar syndrome secondary to multiple sclerosis

Abstract. Cerebellar syndrome is one of the most disabling developments in multiple sclerosis (MS). In neurodegenerative disorders, cerebellar syndrome is thought to be related to a neurochemical deficit of 5-hydroxytryptamine (5-HT). Previous studies found that a levorotatory form of 5-hydroxytryptophan, a 5-HT precursor, and ondansetron, a 5-HT₃ receptor antagonist, decreased cerebellar symptoms in Friedreichs ataxia and MS. We studied the effect of another 5-HT₃ receptor antagonist, dolasetron mesilate, on cerebellar syndrome in MS patients.Thirty-four MS patients were included in a placebo-controlled double-blind crossover study. They received a single dose of intravenous dolasetron mesilate or placebo. A quantitative evaluation of cerebellar syndrome using the nine-hole peg test and an ataxia score comprising static and kinetic parameters were performed before and after each treatment. No statistical difference was observed in the dolasetron mesilate group, compared with the placebo group. There was, however, inter-individual variability in the treatment response.This double-blind study on cerebellar syndrome in MS patients did not confirm the positive effect of dolasetron mesilate suggested by previous studies.     

The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy

BACKGROUND: Olivopontocerebellar atrophy (OPCA) is a chronic neurodegenerative disease with symptoms of cerebellar ataxia, parkinsonism, autonomic disturbances and ophthalmoplegia. Buspirone, a 5-HT1(A) agonist could constitute a symptomatic improvement in cerebellar dysfunction whereas estrogen has been investigated for neuroprotection. We conducted an open-labeled pilot trial to assess the efficacy of estrogen with buspirone treatment. PATIENTS AND METHODS: Eighteen patients (7 male and 11 female) with OPCA were randomized into the buspirone (15 mg/day, n=9), or the combined treatment group (estrogen, 0.625 mg/d plus buspirone, n=9). For the clinical rating, International Cooperative Ataxia Rating Scale (ICARS) was used and dysarthria, gaze evoked nystagmus, finger to nose, pronation-supination alternating movement, knee-tibia test, and gait speed were evaluated for 12 months. RESULTS: Buspirone-treated group showed improvements in finger to nose and pronation-supination alternating movement test (p=0.046 and p=0.025, respectively). The combination group (Estrogen+buspirone), however, showed no improvement in cerebellar sub-scales compared to the baseline. CONCLUSIONS: Buspirone treatment showed feasible efficacies for OPCA, while the combined treatment of estrogen and buspirone failed to improve, suggesting estrogen may not have further benefit in cerebellar dysfunction.     

Comparison of cerebellar ataxias: A three‐year prospective longitudinal assessment

We quantitatively investigated the clinical severity and progression of diseases with ataxia, as measured with the Scale for the Assessment and Rating of Ataxia, and examined the potential application of the Scale for the Assessment and Rating of Ataxia for future therapeutic trials. Severity of ataxia was assessed in 238 patients with spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, spinocerebellar ataxia type 6, spinocerebellar ataxia type 17, multiple system atrophy‐cerebellar variant, or Gerstman‐Sträussler‐Scheinker disease. Among them, 119 (50%) were longitudinally examined three to seven times, in a period of 8 to 38 months, resulting in a total set of 535 assessments. The differences between spinocerebellar ataxia and multiple system atrophy‐cerebellar variant were ascertained cross‐sectionally and longitudinally. Gerstman‐Sträussler‐Scheinker disease had the fastest progression, followed by multiple system atrophy‐cerebellar variant, spinocerebellar ataxia type 17, spinocerebellar ataxia type 3, spinocerebellar ataxia type 2, and spinocerebellar ataxia type 6. Patients with multiple system atrophy‐cerebellar variant had a faster progression in gait, sitting, speech, and total score than patients with spinocerebellar ataxias. For a randomized, case‐control trial, a sample size of 47 for spinocerebellar ataxia and 85 for multiple system atrophy‐cerebellar variant in the treatment or placebo arms would have a sufficient statistical power to demonstrate the efficacy of a new therapy that would retard ataxia progression by 1 point per year as measured by the Scale for the Assessment and Rating of Ataxia. The results will have a significant impact on the planning and implementation of future therapeutic trials of spinocerebellar ataxia and multiple system atrophy‐cerebellar variant. © 2011 Movement Disorder Society     

Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients

BACKGROUND: Antibodies to glutamic acid decarboxylase (GAD-Ab) are described in patients with insulin-dependent (type 1) diabetes mellitus (IDDM), in stiff-man syndrome, and, recently, in a few patients with cerebellar ataxia. OBJECTIVES: To show a link between GAD-Ab and some patients with cerebellar ataxia and to clarify their clinical and immunologic profiles. METHODS: Serum samples were selected from 9000 samples of 4 laboratories. The selection criterion was an immunohistochemical pattern compatible with GAD-Ab that was confirmed by radioimmunoassay. We identified 22 patients with stiff-man syndrome and 14 with cerebellar ataxia and GAD-Ab. RESULTS: Thirteen of the 14 patients with cerebellar ataxia and GAD-Ab were women, and 11 had late-onset IDDM. Patients did not have clinical or radiologic evidence of brainstem involvement. Ten patients had oligoclonal IgG bands in the cerebrospinal fluid, and intrathecal GAD-Ab synthesis was observed in 5 of the 6 patients studied. The level of GAD-Ab of these patients was similar to those with stiff-man syndrome and significantly higher than those with IDDM or with polyendocrine autoimmunity (P<.001). However, the GAD-Ab levels of 6 of the 9 patients with polyendocrine autoimmunity overlapped with those of patients with cerebellar ataxia. CONCLUSIONS: These results suggest a link between high level of GAD-Ab and some cases of cerebellar ataxia, particularly women with IDDM. If high serum levels of GAD-Ab are detected, the cerebrospinal fluid should be evaluated for the presence of oligoclonal IgG bands and intrathecal synthesis of GAD-Ab to further prove an autoimmune origin of the syndrome.     

Statin-associated cerebellar ataxia. A Brazilian case series

BackgroundDrug-induced cerebellar ataxias (DICA) represent an important group of secondary cerebellar ataxias. Herein, we reported a case series of progressive cerebellar ataxia induced by HMG-CoA reductase inhibitors (statins).MethodsObservational study with a Brazilian case series of patients with cerebellar ataxia due to statins use.ResultsWe described four patients with cerebellar ataxia, predominantly gait ataxia, due to statins use. Mean age was 67.5 years old, predominantly male, with several comorbidities, such as dyslipidemia, diabetes mellitus, hypertension, and myocardial revascularization. After statin withdrawal, and treatment with coenzyme Q10 in some patients, progressive improvement of gait ataxia was observed.DiscussionWe presented a case series of four patients with cerebellar ataxia due to statins use, which represents a new rare side-effect of statins, probably related to coenzyme Q10 deficiency.