请章医生指导
　　 章医生您好，我想对我爱人的吃药情况进行调整，能否麻烦您给予指导，谢谢。
　　他2005年确诊为帕金森，当年52岁，现在59岁了还在上班。期间用过金刚烷胺、泰舒达。2008年开始服用雷沙吉林、美多巴，2009年开始服用森福罗、2011年开始用安坦。后随着症状的加重，用药的剂量、种类均有所增加：
　　近半年来的服药情况是：早上（7点半）1mg雷沙吉林一片、0.25g美多巴半片、1mg森福罗半片；下午（2点半）0.25g美多巴和1mg森福罗各半片；晚上(10点左右)纽普罗贴片6mg。另由于长期血脂高一直在吃力平之(每天1粒)。
　　近个把月来药效明显变差。上午9-10点状况还可以，走路说话均还轻松，11点后差些。下午吃药后效果不明显，手脚僵硬，挪步困难，左手左脚抖动增大、声音低哑、面部表情差，常出现刚刚还很正常突然就僵硬了的状况。
　　我想调整他的用药，但不想增加美多巴的用量，相反他用美多巴已经几年了，我想能否减量或停用一段时间。森福罗好像不能与纽普罗贴片同用，因此也想换出。我买了印度唑尼沙胺和美金刚，在原用药量不变的情况下，每天服0.25mg唑尼沙胺已用了18天，效果目前还不明显，从今天开始已将唑尼沙胺增大到每天0.5mg。我的想法是能否只用雷沙吉林、纽普罗、唑尼沙胺和美金刚这几种药来维持他一天的行动。可他目前的症状又不太好，不知能否这样调整，也不知换药后会出现哪些问题，恳请章医生指导。
　　 

　　唑尼沙胺可以抑制左旋多巴上调的免疫和炎症反应问题
　　临床应用Zonisamide(唑尼沙胺）治疗帕金森症的最新机制解释（续）
　　左旋多巴是PD的有效药物，但控制症状的效果会渐差，到底是药的问题，还是疾病的发展，还是什么原因，以下报告可能是其中一个原因。
　　事实上，左旋多巴在应用的时候，会有一个上调免疫和炎症的问题，免疫炎症会造成胶质细胞的活化，引起多巴胺细胞的衰亡，所以如何在应用左旋多巴的时候（除了用雷沙吉兰这只独立的神经保护剂以外），减低免疫和炎症活动，即可以降低疾病进展的速度。
　　最近日本宫崎大学和滨松医科大学的学者从基因技术层面上肯定了唑尼沙胺在联合左旋多巴治疗帕金森症中提供的保护机制，促进神经系统的功能和发展，这是在国际生物学杂志BBRC上的报告，由于有版权（41.95美元），我只能在此出一个提要，有兴趣了解多一点的可以自己去付款下载。
　　
　　Effect of zonisamide co-administration with levodopa on global gene expression in the striata of rats with Parkinson’s disease
　　Yuto Uedaa, Shoko Tokashikia, Ai Kanemarua, Toshio Kojimab, ,
　　a Section of Psychiatry, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
　　b Research Equipment Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
　　Corresponding author. Address: Research Equipment Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu 431-3192, Japan. Fax: +81 53 435 2300.
　　Received 4 October 2012Available online 25 October 2012
　　
　　Abstract
　　The anti-epileptic drug zonisamide is reported to exert beneficial effects in patients with Parkinson’s disease. To elucidate the pathophysiological mechanisms underlying the anti-parkinsonism effects of zonisamide, we examined the effect of zonisamide co-administered with levodopa in the striata of rats with 6-hydoroxydopamine hemiparkinsonism by using a DNA microarray for genome-wide gene expression profiling. We found that the expression of some genes related to metabolism and nervous system development and function were upregulated by zonisamide; expression of these genes was downregulated by levodopa. Furthermore, many genes related to the immune system and inflammation were downregulated by zonisamide, and their expression was upregulated by levodopa. These results indicate that zonisamide has a protective effect when co-administered with levodopa.
　　
　　
　　
　　Highlights
　　► Long-term use of levodopa has been reported to have adverse effects. ► Zonisamide (ZNS) has beneficial effects for patients with Parkinson’s disease (PD). ► We aimed to elucidate the mechanism underlying ZNS’s protective effects against PD. ► Our results indicated neuroprotective effects of ZNS co-administered with levodopa.
　　
　　 

　　回复192楼 章华
　　回复192楼 章华:唑尼沙胺可以抑制左旋多巴上调的免疫和炎症反应问题
　　这是美国哥伦比亚大学神经内科的Phani S,Loike JD,Przedborski S的观点。
　　帕金森疾病中神经变性和炎症的关系。
　　总的论点是，激化的免疫系统引起胶质细胞活化（释放有害物质）导致黑质神经元的损害及丧失。
　　
　　
　　Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S207-9.
　　Neurodegeneration and inflammation in Parkinson’s disease.
　　Phani S, Loike JD, Przedborski S.
　　SourceDepartment of Neurology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
　　
　　Abstract
　　Parkinson’s disease (PD) is characterized by the progressive degeneration of dopamine (DA) neurons of the substantia nigra pars compacta (SNpc) accompanied by a buildup of proteinaceous aggregates termed Lewy bodies (LB). In addition to protein aggregation and the loss of DA signaling, PD is also characterized by an active immune response. T-cell infiltration accompanies activated microglial and astrocytic accumulation in and around the SNpc. Although potentially beneficial, microglial activation is most likely responsible for furthering disease pathology and DA neuron degeneration through the release of harmful substances such as pro-inflammatory cytokines, reactive oxidative species and reactive nitrogen species. Activation of the NF-κB death pathway has been shown to occur following microglial activation related release of Cox-2, IL-1β, and Toll-like receptor activation, resulting in increased degeneration of DA neurons of the SNpc. Blockade of microglial activation can lead to DA neuron protection in animal models of PD; however, clinical application of anti-inflammatory drugs has not yielded similar benefits. Future therapeutic designs must take into account the multifactorial nature of PD, including the varied roles of the adaptive and innate immune responses.
　　
　　Copyright © 2011 Elsevier Ltd. All rights reserved.
　　
　　PMID:22166436[PubMed - indexed for MEDLINE]  

　　回复191楼 若隐
　　回复191楼 若隐:请章医生指导
　　
　　我的意见稍有不同。
　　纽普罗贴片每天6mg,症状如此可见效果欠佳，建议开始减用。
　　美多巴暂不变，森福罗早午各0.75mg饭后,晚上可用0.5mg,能用金刚烷胺的则每次50-100mg,早午各一次，不能用的用美金刚，每次5mg,每天二次，一周后加至每次10mg,每天二次，贴片减至3mg。
　　唑尼沙胺可用25mg,每天二次，必要时可加至75mg即每天三次。
　　VitB6每天三次，每次一片。
　　暂用一周。
　　 

　　感谢章医生
　　
　　谢谢章医生，您的及时回复让我们倍感温暖。今天开始我们将遵照您的处方服用，效果会随时向您报告。 

　　回复196楼 章华
　　回复196楼 章华:唑尼沙胺在延迟运动神经元退化和阻止胶质细胞增殖的研究
　　运动神经元不断退化、胶质细胞活化增殖会导致帕症的不断演变，唑尼沙胺在延迟运动神经元退化和阻止胶质细胞活化增殖的研究。
　　
　　
　　Zonisamide Treatment Delays Motor Neuron Degeneration and Astrocyte Proliferation in Wobbler Mice
　　Takehisa Hirayama, Yasushiro Yoshii, Kiyokazu Kawabe, Ken Ikeda
　　
　　
　　Abstract
　　
　　Background: Zonisamide (ZNS) had multifunctional effects on several kinds of neurons. Little is known about neuroprotective effects of ZNS on motor neurons. We aimed to study whether this drug can attenuate motor neuron degeneration in wobbler mice.
　　
　　Methods: Wobbler mice were injected daily two doses of ZNS (0.2 mg/kg, 2.0 mg/kg, i.p.) or vehicle from aged 3 - 4 weeks at disease onset for more than 4 weeks. Motor function was evaluated by pull-strength and deformity scale of the forelimbs. Those symptomatic assessment and body weight were measured weekly. Neuropathological changes of the biceps muscle and the cervical cord were analyzed at 4 weeks posttreatment.
　　
　　Results: ZNS treatment (2.0 mg/kg) significantly delayed progression of forelimb motor dysfunction compared to vehicle (P less than 0.01). Gain of body weight did not differ statistically between three groups. Higher doses of ZNS administration decreased denervation atrophy in the biceps muscle (P less than 0.01), suppressed loss of motor neurons (P less than 0.01) and inhibited astrocyte proliferation (P less than 0.01).
　　
　　Conclusions: The present study indicated that ZNS treatment attenuated motor neuron degeneration and astrocytosis in the wobbler mouse. This drug may have a therapeutic potential for motor neuron disease.
　　
　　
　　
　　
　　 

　　调药效果给章医生的反馈
　　 章医生好。遵照您的建议(194楼)对我爱人的用药进行了调整(已调药4-5天)，原来僵硬、抖动、迈不开步、行动困难的现象大有改观，现在又可以四处走动了，非常感谢指导。
　　现我还有两点不清楚想再问一下：1、纽普罗已减至3mg下周要停掉吗？2、美金刚不是比金刚烷胺副作用小吗，为什么两者中您首推金刚烷胺呢？
　　另听说您是从厦门出去的，若有机会回厦门的话能告诉我们吗(我的邮箱：1013118737@qq.com)，以便当面请教。 

　　回复197楼 若隐
　　回复197楼 若隐:调药效果给章医生的反馈
　　
　　若隐好！抱歉昨天没有及时回复。
　　目前的药量可以维持一段时间，包括贴片。
　　与金刚烷胺类似的有金刚乙胺和美金刚，但用于帕症的效应上（有效百分比和强度）都比金刚烷胺要弱。
　　所以首选是金刚烷胺，只有在服用金刚烷胺出现视力和排尿问题、下肢水肿、网状青斑等副作用，或者兼有记忆认知问题，才会建议用美金刚。
　　有机会大家一定见见面。
　　 

　　回复198楼 章华
　　回复198楼 章华
　　
　　谢谢章医生指导。我会按您的医嘱坚持给他用药，有情况会随时向您汇报。也期盼早日见到您。 

　　服用唑尼沙胺的体验
　　 章医生好？自从12月5日改服50mg唑尼沙胺.，13日下午发现每天按时到达的异动及大起大落的开关现象，今天
　　
　　
　　没发生。直到现在基本上平稳，身上轻松，晚上睡觉也能翻身了，虽然还有些吃力。
　　但是在心情不好，情绪激动，动脑劳累时，还是有感觉。
　　章医生，这个药是不是用长了人体也会产生耐药性，不管用了？