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[肉毒杆菌毒素治疗多发性硬化症患者的髋内收肌痉挛]

[Botulinum toxin treatment of hip adductor spasticity in multiple sclerosis].

作者信息

Wissel J, Entner T

机构信息

Universitätsklinik für Neurologie, Innsbruck, Osterreich.

出版信息

Wien Klin Wochenschr. 2001;113 Suppl 4:20-4.

Abstract

Spasticity results in a resistance to passive movement and decrease of passive mobility of the involved joints and is defined as a state of hypertonicity with exaggeration of tendon reflexes mediated by a loss of inhibitory control of upper motor neurons. In patients with severe stages of multiple sclerosis (MS) spasticity of the lower limbs often leeds to a spastic pattern with hip adduction resulting in decreased range-of-motion (ROM), increased pain, spasms, and functional disability (disturbed gait and sitting position) as well as difficulties with perineal hygiene. Local botulinum toxin type A (Btx-A) injections in spastic muscles offer a new treatment approach for managing spasticity and associated problems. Up to now Btx-A is approved for the treatment of blepharospasm and cervical dystonia and the treatment of equinous gait in children with cerebral palsy in Austria and Germany. Up to now only in Switzerland Botox is licensed for the treatment of focal spasticity. Btx-A is a neurotoxin derived from Clostridium botulinum. In most european countries Btx-A is available as Dysport (vial = 500 units) and Botox (vial = 100 units). In prospective studies a ratio of 1 unit Botox to 3-4 units Dysport was found. Following intramuscular injection Btx-A blocks the release of acetylcholine at the neuromuscular junctions, thereby inhibiting muscle contraction, and decreases spastic muscle tone and muscle spindles afferent information to the spinal cord. The spectrum of side effects includes local weakening of the injected and adjacent muscles as well as pain and haematoma at the injection site. At therapeutic doses side effects are local and transient. According to a double blind, placebo controlled, dose ranging study published by Hyman et al. (2000, Dysport in a dose of 500, 1000 and 1500 units reduced the degree of hip adductor spasticity associated with MS, and this benefit was evident despite concomitant use of oral antispasticity medication. According to the results of the study there was a clear trend towards greater efficacy and duration of effects with higher doses of Dysport. Taking efficacy and adverse events into account (incidence of muscle weakness was higher for the 1500 units group than for placebo) the optimal dose for hip adductor spasticity seems to be 1000 units Dysport divided between the adductor magnus, longus and brevis muscles and between both legs. To increase Btx-A effects following injection of hip adductors additional physiotherapy and casting or orthosis to increase passive hip-abduction is recommended. According to the literature anatomical localisation of the adductor muscles for injection and aspiration following insertion of the needle, to avoid injection of the toxin into a vessel, should be performed. A maximum dose of 1500 units Dysport (400 units Botox) per treatment session and 250 units Dysport (50 units Botox) per injection site is recommended. See table for dose-range of Dysport, and Botox in the treatment of adult patients with hip-adductor spasticity. For evaluation of treatment effects in hip adductor spasticity clinical examination with specific scales and measurements (see Appendix) at baseline, 4 and 12 weeks following BtxA injection is recommended:--Global rating of severity (0-4; patient's self assessment and physician's rating) --Global rating of response (-4 - +4; patient's self assessment and physician's rating)--Visual Analogue Scale (patient's self assessment of pain)--Active and passive ROM (manual goniometer)--Distance between the medial femur condyles in thigh extension (distance in cm)--Modified Ashworth scale (0-4)--Ten meter walking time (seconds)--Functional Ambulation Categories (0-5)--Score of perineal hygiene (0-5).

摘要

痉挛会导致对被动运动产生抵抗,受累关节的被动活动度降低,其定义为一种张力亢进状态,伴有上运动神经元抑制控制丧失所介导的腱反射亢进。在多发性硬化症(MS)的严重阶段,患者下肢痉挛常导致一种痉挛模式,伴有髋关节内收,从而导致活动范围(ROM)减小、疼痛加剧、痉挛以及功能残疾(步态和坐姿紊乱),还会出现会阴卫生护理困难。在痉挛肌肉中局部注射A型肉毒杆菌毒素(Btx-A)为处理痉挛及相关问题提供了一种新的治疗方法。到目前为止,Btx-A已被批准用于治疗眼睑痉挛和颈部肌张力障碍,在奥地利和德国还被批准用于治疗脑瘫患儿的马蹄内翻足步态。到目前为止,仅在瑞士,保妥适被批准用于治疗局灶性痉挛。Btx-A是一种源自肉毒杆菌的神经毒素。在大多数欧洲国家,Btx-A有两种产品可供使用,分别是丽舒妥(每瓶500单位)和保妥适(每瓶100单位)。在前瞻性研究中发现,保妥适与丽舒妥的单位换算比例为1:3 - 4。肌内注射后,Btx-A会阻断神经肌肉接头处乙酰胆碱的释放,从而抑制肌肉收缩,降低痉挛肌肉的张力以及减少向脊髓的肌梭传入信息。副作用包括注射部位及相邻肌肉的局部无力,以及注射部位的疼痛和血肿。在治疗剂量下,副作用是局部性且短暂的。根据海曼等人(2000年)发表的一项双盲、安慰剂对照、剂量范围研究,500、1000和1500单位剂量的丽舒妥可降低与MS相关的髋关节内收肌痉挛程度,即便同时使用口服抗痉挛药物,这种益处依然明显。根据该研究结果,随着丽舒妥剂量增加,疗效和作用持续时间有明显增大的趋势。综合考虑疗效和不良事件(1500单位组的肌肉无力发生率高于安慰剂组),治疗髋关节内收肌痉挛的最佳剂量似乎是1000单位丽舒妥,分别注射于大收肌、长收肌和短收肌,双侧下肢均需注射。为增强注射髋关节内收肌后Btx-A的效果,建议额外进行物理治疗,并使用支具或矫形器以增加髋关节被动外展。根据文献,注射时应明确内收肌的解剖定位,并在进针后进行回抽,以避免将毒素注入血管。建议每次治疗的最大剂量为1500单位丽舒妥(400单位保妥适),每个注射部位的最大剂量为250单位丽舒妥(50单位保妥适)。见表中丽舒妥和保妥适治疗成年髋关节内收肌痉挛患者的剂量范围。为评估髋关节内收肌痉挛的治疗效果,建议在注射Btx-A前、注射后4周和12周使用特定量表和测量方法进行临床检查(见附录):

  • 严重程度总体评分(0 - 4;患者自我评估和医生评分)

  • 反应总体评分(-4 - +4;患者自我评估和医生评分)

  • 视觉模拟量表(患者自我疼痛评估)

  • 主动和被动活动范围(手动量角器测量)

  • 大腿伸展时内侧股骨髁之间的距离(厘米)

  • 改良Ashworth量表(0 - 4)

  • 十米步行时间(秒)

  • 功能性步行分类(0 - 5)

  • 会阴卫生评分(0 - 5)

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