阿米三嗪-萝巴新治疗耳蜗前庭疾患的疗效及安全性

目的　评价阿米三嗪 萝巴新治疗耳蜗前庭疾患的疗效及安全性。方法　多中心开放自身对照研究。 2 3个中心 6 6 2例门诊眩晕患者入选 ,伴或不伴耳鸣。所有患者均应用阿米三嗪 萝巴新 1片 ,每日 2次 ,连续使用 3个月 ,评估治疗前、治疗 1个月、治疗 3个月眩晕、眼震、耳鸣情况变化 ,伴听力下降者随访电测听结果。研究结束时由患者和医师分别评价总体疗效 ,记录所有不良反应。结果　治疗前、治疗 1个月、治疗 3个月眩晕、眼震、耳鸣 0～ 3级病例数经F检验差异有非常显著意义 (眩晕严重程度F =2 2 0 1 6 4 ,眩晕持续时间F =10 31 4 7,眩晕发作频率F =10 35 38,眼震F =132 4 14 ,耳鸣F =80 7 0 4 ,均P <0 0 1)。 10 4例电测听异常患者在治疗 1个月、治疗 3个月分别有2 0 2 %、30 8%转为正常 (F =30 4 7,P <0 0 1)。阿米三嗪 萝巴新能明显改善患者的眩晕、眼震、耳鸣及电测听检查结果。治疗前后、治疗 1个月与 3个月之间差异有非常显著意义 (P <0 0 1)。研究者及患者总体疗效评价好。不良反应发生率治疗 1个月时为 1 98% ,3个月时为 1 11%。结论　阿米三嗪 萝巴新是一个治疗耳蜗前庭疾患的有效、安全药物。     

阿米三嗪-萝巴新治疗轻度血管性痴呆的疗效和安全性

目的评价阿米三嗪．萝巴新治疗轻度血管性痴呆（VD）的疗效和安全性。方法采用多中心、开放、自身对照试验研究方法，对128例临床诊断为轻度可能的VD患者，给予口服阿米三嗪-萝巴新，每日2片，早晚各1片。分别于服药前及服药后6周和12周，采用简易精神状态（MMSE）量表、AD评估量表-认知部分、Mattis痴呆评价（CDR）量表、日常生活能力（ADL）量表等神经心理分析工具对轻度VD患者的记忆力、注意力、定向力、语言能力、执行能力及生活能力进行评价，并观察有无恶心、头晕等副作用，进行安全性评估。结果经过3个月阿米三嗪-萝巴新治疗，轻度VD患者的MMSE评分（治疗前16．98，治疗后17．97，P〈0．05），CDR评分（治疗前1．43，治疗后1．21，P〈0．01），ADAS总分（治疗前35．12，治疗后33．08，P〈0．05）以及ADAS因子分中的记忆力和定向力评分、语言能力评分、实践能力评分和ADL评分（治疗前45．55，治疗后43．41，P〈0．01）均有明显改善。阿米三嗪-萝巴新的安全性和依从性良好，在研究期间，3例患者出现皮疹，1例患者因药物作用不明显退出研究，不良事件发生率为2．3％。结论阿米三嗪-萝巴新可以改善轻度VD的认知功能，提高患者的生活能力，且药物的安全性好。     

阿米三嗪-萝巴新对慢性间断性缺氧大鼠学习记忆能力的改善及相关生化机制的探讨

目的　探讨阿米三嗪 萝巴新 (almitrine raubasine)对慢性间断性缺氧 (chronicepisodichypoxia ,EHYP)大鼠学习记忆能力和脑内胆碱乙酰转移酶 (cholineacetyltransferase ,ChAT)活性的影响 ,为寻找改善阻塞性睡眠呼吸暂停 (OSAS)患者学习记忆障碍的方法提供实验依据。方法　建立EHYP大鼠模型 (EHYP组 ,9只 ) ,并给予阿米三嗪 萝巴新 (0 0 3片 / 2 5 0 g体重 ,每天 2次 )干预(治疗组 ,9只 ) ,并设不行缺氧处理大鼠为对照组 (7只 )。用被动避暗回避反射试验评价大鼠学习记忆能力 ,潜伏期 (STL)越长 ,学习记忆能力越强 ;用放射化学法测定大鼠皮层、海马和纹状体ChAT活性。结果　与对照组相比 ,EHYP组大鼠STL明显短于对照组和治疗组 (P <0 0 1) ,各脑区ChAT活性明显低于对照组和治疗组 (均P <0 0 1)。结论　阿米三嗪 萝巴新可改善EHYP大鼠学习记忆能力并提高其脑内ChAT活性。     

血管舒缩功能变化在急性脑梗死发病中的作用及阿米三嗪-萝巴新的干预

急性脑梗死中无疑存在血管功能异常,直接的证据可以从脑梗死的概念中得到。我们选取血管内皮细胞分泌的具有代表性的两种影响血管舒缩功能的细胞因子,观察它们在急性脑梗死中的变化及其相互关系,并给予阿米三嗪 萝巴新干预,以探讨血管舒缩功能变化在脑梗死病因中的作用并寻找相应对策。资料和方法1.研究对象与分组:研究对象分为脑梗死常规治疗组、脑梗死常规加阿米三嗪 萝巴新治疗组、脑梗死高危组和健康对照组。脑梗死组为急性脑梗死住院患者,共收集到10 8例,均为3日内发病的住院患者,平均年龄(6 0 0±6 8)岁,男性6 2例,女性4 6例,利用随…     

无症状性脑梗死对首发急性缺血性卒中患者认知功能的影响

目的 观察无症状性脑梗死(silent cerebral infarction,SCI)对首发急性缺血性卒中患者认知功能的影响.方法 连续纳入起病14 d内的首发急性缺血性卒中患者,依据MRI将患者分为急性缺血性卒中伴随SCI和不伴随SCI两组.认知功能评定采用北京版蒙特利尔认知评估(Montreal cognitive assessment,MoCA)量表和简明智力状态检查(mini-mental state examination,MMsE)量表,分别在卒中后2周及3个月进行.结果 急性缺血性卒中早期和3个月,SCI组与非SCI组非痴呆性血管性认知功能损害比例分别为(54.7%、76.4%;54.1%、66.7%),血管性痴呆比例分别为(28.3%、11.8%;13.5%、7.4%),MoCA评分中位数分别为(19、22;22、25),P值均>0.05;SCI病灶数量是卒中后3个月痴呆的危险因素(OR=1.22,95% CI 1.02～1.45):卒中后3个月SCI组总体认知功能及视空间执行功能、注意力和抽象思维能力无显著改善,P值均>0.05.结论 SCI病灶数量是首发急性缺血性卒中后3个月痴呆的危险因素,SCI影响患者认知功能的改善.     

抗抑郁治疗对老年脑卒中后抑郁及康复的影响

目的:观察抗抑郁治疗对老年缺血性脑卒中后抑郁症状及神经功能康复的作用.方法:将老年脑卒中后抑郁患者356例分为文拉法辛组128例、阿米替林组116例及对照组112例,于治疗前后进行汉密尔顿抑郁量表(HAMD)和神经功能缺损量表(CSS)、日常生活能力量表(ADL)评定.结果:文拉法辛组和阿米替林组治疗第2周HAMD评分和第12周CSS评分较治疗前和对照组均明显降低;文拉法辛组和阿米替林组3个月后ADL亦明显改善(P均＜0.05),但阿米替林组不良反应明显高于文拉法辛组.结论:抗抑郁治疗有利于老年脑卒中后抑郁患者神经功能康复,提高生活能力,减少并发症.     

56例老年血管性痴呆病人的护理体会

本文对56例老年血管性痴呆病人进行护理,现将护理体会总结如下. 1 临床资料 1.1 一般资料 样本来自我院2007-01～2009-10住院的老年血管性痴呆患者,以Hachinski缺血评分量表>分及长谷川智能量表(HDS)<24分者为老年血管性痴呆诊断标准[1],病程≥3个月;由照料者或知情者提供信息,意识清晰,检查合作,排除其他原因引起的痴呆,入组56例,男31例,女25例,年龄62～76岁,平均(78.2±15.3)岁;其中有高血压和动脉粥样硬化史34例(62.7%),反复卒中进入痴呆38例(32.6%),1次卒中起病7例(8.1%),糖尿病26例(40.7%),高血脂19例(22.1%).     

脑血运重建治疗缺血性烟雾病手术时机的选择

目的探讨脑血运重建术治疗缺血性烟雾病的最佳手术时机。方法回顾性分析武汉大学人民医院2016年7月—2018年5月收治的41例缺血性烟雾病患者的临床资料。所有患者均行颞浅-大脑中动脉搭桥+颞肌贴敷术,依据缺血性卒中发生时间与手术之间的时间间隔,将患者分为早期组(1～3个月,17例)和晚期组( 3个月,24例)。分析比较两组患者术后3个月脑灌注改善率及神经功能缺损恢复状况;以及术后并发症(脑出血、脑梗死、过度灌注)的发生率。结果与晚期组相比,早期组患者术后3个月的脑灌注改善率更高,美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分明显降低,差异均有统计学意义(P 0. 001,P=0. 01)。术后总的并发症(包括过度灌注、脑出血、脑梗死)发生率,早期组为52. 9%,晚期组为54. 2%,两组的差异无统计学意义(P 0. 05)。结论缺血性烟雾病患者卒中事件后1～3个月内行脑血运重建术,对于改善患者脑灌注和神经功能恢复更有效,并且不增加术后并发症发生的风险。     

卡托普利上调缺血性脑卒中患者血小板一氧化氮合酶的实验和临床研究

目的　研究卡托普利对缺血性脑卒中患者血小板一氧化氮合酶 (NOS)的上调及临床应用。方法　测定急性缺血性脑卒中患者及健康体检者的血小板NOS及在体外加氧化低密度脂蛋白 (oxLDL)、卡托普利后血小板NOS的活性 ;检测患者服卡托普利前、服后 1个月及 3个月的血浆oxLDL、NOS、一氧化氮 (NO) ,血小板NOS、NO ,同时检查神经功能。结果　 (1)卒中组和对照组血小板加oxLDL后 ,NOS值均明显下降 (P <0 .0 1) ,卒中组下降更明显 ;(2 )两组血小板同时加卡托普利、oxLDL后 ,NOS值均明显升高 (P <0 .0 1) ,卒中组升高更明显 ;(3)两组血小板单纯加卡托普利后 ,其NOS值均明显升高 (P <0 .0 1) ,同样亦是卒中组升高更明显 ;(4 ) 4 0例缺血性脑卒中患者服用卡托普利后血浆oxLDL明显下降 ,血小板NOS、NO ,血浆NOS、NO明显增高 ,神经功能明显改善。结论　卡托普利有直接上调血小板NOS的作用 ,卡托普利通过提高血小板NOS活性的作用 ,可以改善内皮功能 ,防治脑卒中     

65例老年脑血管病的临床研究

目的了解脑血管性痴呆中各项因素对病程及预后的影响。方法方法使用长谷川痴呆量表（HDS）测试,将住院的65例符合诊断的脑血管病患者分成痴呆组与非痴呆组,进行精神、神经症状、体征、CT、病程、卒中发作史等的对照观察,为期半年。结果两组患者症状仅在失用、主动性差、表情呆滞存在差异P〈0．01;CT比较痴呆组复发性脑梗死18例,非痴呆组单发脑梗死21例;两组患者病程在4年以上的人数比较之间有显著性差异P〈0．05;痴呆发生率在卒中1次发作为27．7％,2次发作为44．8％,3次发作为77．7％;治疗后痴呆组与非痴呆组HDS测查分别提高1．4、1．6分。结论痴呆组与非痴呆组的症状与大脑痛变的大小、部位有关,多次发作梗塞是造成痴呆的主要因素,病程越长痴呆发生率越高。     

Early fluoxetine treatment of post-stroke depression

Objective: Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery. This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients. Methods: This double-blind, randomized placebo-controlled study was of patients within two weeks after stroke. Moderate to severe depressed patients (determined by Hamilton Depression Scale (HDS) > 15, the Beck Depression Inventory (BDI) and the Clinical Global Impression (CGI) Scale) were randomized to receive either 20 mg/d fluoxetine or placebo for 3 months. Beside the psychiatric assessment, patients were evaluated by use of the Scandinavian Stroke Scale (SSS), the Mini-Mental-State-Examination (MMSE) and the Barthel-Index (BI). An open-label long-term follow up was done 18 months after the initial assessment. Results: 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke. 50 patients completed the trial per-protocol. The initial severity of depression was comparable in the two groups (mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group), as were neurological symptom severity and demographic parameters. Significant improvement was seen in both groups within 4 weeks of treatment, whereas no advantages of fluoxetine could be observed at this time. This indicates a high degree of spontaneous recovery during early rehabilitation therapy. BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks, whereas the scores increased again in the placebo group. This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion, when patients who had been treated with fluoxetine were significantly less depressed. No side effects of fluoxetine treatment were detected. Conclusions: The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion, but could not be demonstrated within the first three months of controlled treatment. The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious. Fluoxetine treatment was well tolerated and safe. Received: 5 February 2002, Received in revised form: 8 October 2002, Accepted: 28 October 2002 Correspondence to Stefan Fruehwald, MD     

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke – a randomized,double‐blind,placebo‐controlled trial

Lokk J, Salman Roghani R, Delbari A. Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke – a randomized, double‐blind, placebo‐controlled trial.
Acta Neurol Scand: 2011: 123: 266–273.
© 2010 John Wiley & Sons A/S. Objective – Amphetamine‐like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. Material and methods – A randomized, double‐blind, placebo‐controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl‐Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. Results – All participants showed recovery of motor function and ADL during treatment and at 6‐month follow‐up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6‐month follow‐up. Conclusion – Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most.     

小剂量替罗非班与双抗治疗进展性脑卒中的疗效对比及安全性评价

目的对比替罗非班和双抗治疗进展性脑卒中的疗效,并评价其临床安全性。方法选取2015-07—2016-10我院神经内科确诊的60例急性进展性脑梗死患者,且1周内病情进展,神经功能缺损较前加重。其中28例采用小剂量替罗非班治疗后接受双抗治疗为实验组,32例仅接受双抗治疗为对照组。治疗3d、7d后,比较2组NIHSS评分、BI指数、血小板计数、各项出凝血指标及出血等并发症。结果治疗3d后2组NIHSS评分差异有统计学意义(P0.05),BI指数差异无统计学意义(P0.05);治疗7d后2组间NIHSS评分及BI指数差异有统计学意义(P0.05)。结论替罗非班治疗进展性脑卒中的疗效显著,安全性良好,可提高患者预后质量。     

Evaluating the efficacy of acupuncture in defined aspects of stroke recovery

OBJECTIVE: To investigate the efficacy of acupuncture on stroke recovery compared to an inert placebo. DESIGN : Placebo-controlled, randomised, clinical trial. SETTING: Post-stroke rehabilitation wards in five NHS hospitals in the UK. SUBJECTS: Patients between 4 and 10 days after their first stroke. INTERVENTIONS AND OUTCOME MEASURES: The patients received 12 acupuncture or placebo treatments over four weeks. Acupuncture with electrical stimulation was compared with mock TENS, and assessments continued for 12 months after entry. Primary outcome was the Barthel Index (BI). Secondary outcomes were muscle power, Motricity Index (MI), mood, Nottingham Health Profile (NHP) and treatment credibility. RESULTS: 92 patients completed data sets. Data were analysed using both t tests and a structural equation based on longitudinal analysis of both BI and MI, using generalised estimating equations with an exchangeable correlation structure. While both acupuncture and placebo (mock TENS) appeared to have had an equal effect on stroke recovery, there is no significant difference between the two interventions at 12 (p = 0.737, 95 % CI -2.00 to 2.81) and 52 weeks (p = 0.371, 95 % CI -3.48 to 1.32). An apparently accelerated improvement in the MI scores in the acupuncture group at 3 weeks (p = 0.009, 95 % CI 1.55 to 10.77) is interesting. CONCLUSIONS: Acupuncture did not demonstrate specific efficacy over placebo and both groups did as well as normally expected with this condition.     

Long-term follow-up after extracranial internal carotid artery dissection

OBJECTIVE: To evaluate long-term outcome after extracranial internal carotid artery dissection (eICAD) in consideration of the applied antithrombotic therapy. MATERIAL AND METHODS: Among 33 consecutive eICAD patients initially treated either with anticoagulation (n = 25) or with antiplatelets (n = 8), a standardized interview was performed after 28 +/- 22.1 months to analyze risks and benefits of both agents. Ischemic and hemorrhagic complications, occurrence of seizure and rates of arterial recanalization were compared and long-term clinical outcome was assessed using the modified Rankin Scale (mRS) and Barthel Index (BI). RESULTS: Among anticoagulated patients, 1 died due to brain herniation. In 3 patients stroke (n = 2) or TIA (n = 1) recurred. In the antiplatelet group, none died and no subsequent ischemic events happened. Hemorrhagic complications were noted in neither treatment group. Functional outcome among anticoagulated patients was BI 92 +/- 21.6 and mRS 1.48 +/- 1.50, which did not differ from patients initially treated with antiplatelets (BI 89 +/- 18.9, mRS 1.50 +/- 1.41, p > 0.05). Four anticoagulated patients developed seizures, compared to 2 patients with antiplatelets (p > 0.05). Arterial recanalization occurred in 16 of 22 antico- agulated patients with ultrasound follow-up, compared to 6 of 6 patients with antiplatelets (p > 0.05). CONCLUSION: In the absence of iatrogenic side effects, both anticoagulation and antiplatelets seem to be safe for eICAD. The rates for death and stroke were low and outcome ratings did not differ between both agents. These findings may indicate that a controlled randomized trial comparing anticoagulation and antiplatelets is ethically justified.     

A double blind placebo RCT to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients

Motor excitability is increased in both hemispheres in stroke patients during motor recovery. Pharmacologically controlled changes of cortical excitability might be beneficial for synaptic plasticity and therefore facilitate functional recovery after a brain lesion. In particular, it has been suggested that antidepressant drugs can modulate motor excitability. Several recent reports suggest the possibility of monitoring pharmacological effects on brain excitability through transcranial magnetic stimulation (TMS). The aim of this study was to investigate motor area excitability in patients with stroke after oral administration of citalopram. We conducted a prospective randomised placebo controlled study. Twenty patients with unilateral stroke were included in the study: ten patients treated by antidepressive drug and ten patients with placebo. A selective serotonergic drug (citalopram) or a placebo was administered using a mean dosage of 10 mg/day in combination with physiotherapy. Motor cortex excitability was studied by single and paired transcranial magnetic stimulation. TMS recording was tested before (T1) and 1 month after (T2) beginning drug treatment. Patients treated by the serotonergic drug, compared to patients that received a placebo, showed a significant improvement in neurological status as measured by NIHSS and a decrease of motor excitability over the unaffected hemisphere, while no differences were observed over the affected hemisphere. Our findings suggest that treatment with serotonergic drugs can bring about a significant decrease of the motor cortex excitability in stroke patients with effects on both the affected and unaffected hemispheres associated with a better motor recovery. M. Acler and P. Manganotti equally participated to the work.     

A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM

OBJECTIVE: To investigate whether the combination of intravenous immunoglobulin (IVIg) with prednisone improves muscle strength and alters endomysial inflammation in patients with sporadic inclusion body myositis (s-IBM). BACKGROUND: In a previous controlled trial in s-IBM, IVIg did not significantly improve strength in spite of modest benefits in some muscle groups. The possibility that prednisone may have a synergistic effect with IVIg prompted another controlled trial. METHODS: Thirty-six patients with biopsy-proven IBM were randomized to receive IVIg or placebo monthly for 3 months. Before infusions, all patients were started on high-dose prednisone for 3 months. Primary outcome measures were differences in the 1) Quantitative Muscle Strength (QMT) testing; and 2) modified Medical Research Council (MRC) scores, between the patients randomized to IVIg + prednisone compared with those randomized to placebo + prednisone. Repeated open muscle biopsies were performed at random in 24 patients to determine changes in the number of autoinvasive T cells and necrotic muscle fibers. RESULTS: Nineteen patients were randomized to IVIg + prednisone and 17 to placebo + prednisone. No significant change was noted in muscle strength, assessed by QMT and MRC, from baseline to the 2nd, 3rd, or 4th month after treatment between the two groups. The number of necrotic fibers was reduced in the IVIg randomized group (p < 0.01), and the mean number of CD2+ cells was significantly decreased in both groups (p < 0.0001), denoting a steroid effect. CONCLUSION: IVIg combined with prednisone for a 3-month period was not effective in IBM. Endomysial inflammation was significantly reduced after treatment, but the reduction was not of clinical significance.     

Type I interferons and the quality of life of multiple sclerosis patients. Results from a clinical trial on interferon alfa-2a.

The objective of the study was to examine whether the beneficial effect of treatment of interferon alfa-2a on multiple sclerosis seen by magnetic resonance imaging is reflected in a corresponding improvement in the quality of life (QoL) and to address the impact of adverse events related to this treatment on the QoL. The study was a randomised double-blinded placebo-controlled treatment trial including 97 relapsing-remitting multiple sclerosis patients. Thirty-two patients received 4.5 MIU recombinant interferon alfa-2a, 32 patients received 9.0 MIU recombinant interferon alfa-2a and 33 patients received placebo treatment for 6 months. All patients were followed up 6 months after end of treatment. QoL was assessed according to the eight scales of the SF-36 Health Survey and measured at baseline, month 3, 6 and 12. The effect found on MRI was not reflected in a corresponding change in the QoL. We found a relationship between the presence of new enhancing lesions and reduced QoL among the placebo patients, whereas this was not found among the patients treated with interferon. The presence of the adverse events fatigue, myalgia, headache and weakness were significantly negatively correlated to several of the QoL dimensions. Conclusively, the treatment with interferon alfa-2a does not seem to improve the patients' QoL after 6 months of treatment, in spite of a marked effect measured by MRI. The treatment is followed by adverse events that negatively affected the QoL.     

Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group

A randomized, controlled trial of daily prednisone was conducted in 99 boys (aged 5 to 15 years) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment. Prednisone at 0.3 mg/kg (n = 33), prednisone at 0.75 mg/kg (n = 34), and placebo (n = 32) were administered for 6 months. Patients were examined using manual muscle and myometry testing, timed functional testing, pulmonary function testing, and laboratory measurements at 10 days, 1 month, 2 months, 3 months, and 6 months of treatment. Boys treated with prednisone had stronger average muscle strength scores, than did boys treated with placebo as early as 10 days after starting therapy. At the 3-month visit, the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone, indicating a dose response. At 6 months, significant side effects occurred in the group treated with 0.75 mg/kg of prednisone, including weight gain, cushingoid appearance, and excessive hari growth. Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg. Importantly, no side effects were evident at 10 days or 1 month of treatment, despite improvement in muscle strength and function. We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less.     

A double-blind, randomized, controlled study of oral pirfenidone for treatment of secondary progressive multiple sclerosis

Currently, there are no approved treatments for secondary progressive multiple sclerosis (MS) that stabilize or reverse the neurological disabilities associated with this disease. Oral pirfenidone was found to stabilize and overcome the disabilities in two published independent open-label studies in secondary progressive MS. This led us to study pirfenidone in a phase II double-blind, randomized and controlled, clinical trial in patients with advanced secondary progressive MS for 12 months. Forty-three patients met the eligibility criteria approved by the IRB and accepted by the FDA. Of these patients, 18 were randomly assigned to placebo and 25 patients to oral pirfenidone groups. All eligible patients were included in the statistical analysis of the data according to intention-to-treat principles. Some patients on oral pirfenidone manifested mild drug-related adverse effects, but it was well tolerated overall. By one month, pirfenidone significantly (P < 0.05) improved the Scripps Neurological Rating Scale (SNRS) scores, and scores remained significantly improved for 3, 6 and 12 months when compared to the baseline SNRS scores. In contrast, the SNRS scores of patients on oral placebo were not significantly improved at 1, 3, 6 or 12 months of the study, when compared with baseline scores. Oral pirfenidone significantly (P <0.04) reduced the incidence of relapses (27.8% on placebo versus 8.0% on pirfenidone). Furthermore, oral pirfenidone treatment was associated with a marked improvement in bladder dysfunction (40.0% on pirfenidone versus 16.7% on placebo). Expanded Disability Status Scale scores and MRI lesion count were not significantly different in the placebo and pirfenidone groups. These findings indicate a significant effect of pirfenidone on clinical disability and bladder function for secondary progressive MS patients. A major multicentre, double-blind, randomized, controlled trial is justified.