Mathew Ninan T, Kailasam Jayasree, Meadors Lori
Houston Headache Clinic, Houston, TX 77004, USA.
Headache. 2008 Feb;48(2):194-200. doi: 10.1111/j.1526-4610.2007.00914.x. Epub 2007 Sep 12.
To evaluate predictors of response to botulinum toxin type A (BoNTA; BOTOX, Allergan Inc., Irvine, CA, USA) in patients with chronic daily headache (CDH).
Chronic migraine (CM) and chronic tension-type headache (CTTH) form the majority of CDH disorders. Controlled trials indicate that BoNTAis effective in reducing the frequency of headache and number of headache days in patients with CDH disorders. A recent migraine study found that patients with imploding or ocular types of headaches were responders to BoNTA, whereas those with exploding headaches were not. To date, there are no data on factors that might predict response to BoNTA in patients with CDH.
A total of 71 patients with CM and 11 patients with CTTH were treated with 100 units BoNTA. Every patient received at least 2 sets of injections at intervals of 12-15 weeks; fixed sites, fixed dose, and "follow-the-pain" approaches were used for the injections. A detailed medical history was taken for each patient in addition to recording Migraine Disability Assessment Scale (MIDAS) scores at baseline and every 3 months after each set of injections. Headache frequency was assessed throughout the study from baseline to weeks 24-27. Patients recorded the frequency, severity, and duration of headaches in Headache Diaries. Patients were divided into responders (> or = 50% reduction in both headache frequency and MIDAS scores compared with baseline) and nonresponders (< 50% reduction in either of the above variables). Variables analyzed for predictors of response include headache that is predominantly unilateral or bilateral in location, presence of cutaneous allodynia (scalp allodynia), and presence of pericranial muscle tenderness (also referred to as muscle allodynia). Chi-square analysis was used for parallel-group comparisons (proportion of CM responders vs proportion of CM nonresponders and proportion of CTTH responders vs proportion of CTTH nonresponders).
In the CM group, 76.1% (54 /71) of patients were responders to BoNTA, of which 68.5% (37/54) had headache that was predominantly unilateral in location and the remaining 31.5% (17/54) had headache that was predominantly bilateral in location (both P < .01 vs CM nonresponders). Of the 23.9% (17/71) CM nonresponders, 76.5% (13/17) reported predominantly bilateral headache and in the remaining 23.5% (4/17) the headache was unilateral. In the CM responders group, 81.5% (44/54) had clinically detectable scalp allodynia, while pericranial muscle tenderness was present in 61.1% (33/54) (both P < .01 vs CM nonresponders). The presence of scalp allodynia and pericranial muscle tenderness in the CM nonresponders was 11.8% (2/17) and 17.6% (3/17), respectively. In the CTTH group where all patients (100%, 11/11) had bilateral headache, 36.4% (4/11) of patients were responders to BoNTA. All of those CTTH responders (100%, 4/4) had pericranial muscle tenderness (P < .05 vs CTTH nonresponders). None of the CTTH nonresponders had pericranial muscle tenderness. No clinically significant serious adverse events (AEs) were reported. Mild AEs, eg, injection-site pain that persisted for 1-9 days, were reported in 11 patients. One patient had transient brow ptosis.
A greater percentage of patients with CM responded to BoNTA than patients with CTTH. Headaches that were predominantly unilateral in location, presence of scalp allodynia, and pericranial muscle tenderness appear to be predictors of response to BoNTA in CM, whereas in CTTH, pericranial muscle tenderness may be a predictor of response.
评估慢性每日头痛（CDH）患者对A型肉毒毒素（BoNTA；保妥适，美国加利福尼亚州欧文市艾尔建公司生产）反应的预测因素。
慢性偏头痛（CM）和慢性紧张型头痛（CTTH）构成了大多数CDH疾病。对照试验表明，BoNTA可有效减少CDH疾病患者的头痛频率和头痛天数。最近一项偏头痛研究发现，内爆型或眼型头痛患者对BoNTA有反应，而爆发型头痛患者则无反应。迄今为止，尚无关于CDH患者中可能预测对BoNTA反应的因素的数据。
71例CM患者和11例CTTH患者接受了100单位BoNTA治疗。每位患者至少接受2组注射，间隔12 - 15周；注射采用固定部位、固定剂量和“循痛”方法。除了在基线以及每组注射后每3个月记录偏头痛残疾评估量表（MIDAS）评分外，还为每位患者采集了详细的病史。在整个研究过程中，从基线到第24 - 27周评估头痛频率。患者在头痛日记中记录头痛的频率、严重程度和持续时间。患者被分为反应者（与基线相比，头痛频率和MIDAS评分均降低≥50%）和无反应者（上述任何一个变量降低<50%）。分析反应预测因素的变量包括主要为单侧或双侧位置的头痛、皮肤异常性疼痛（头皮异常性疼痛）的存在以及颅周肌肉压痛（也称为肌肉异常性疼痛）的存在。采用卡方分析进行平行组比较（CM反应者比例与CM无反应者比例以及CTTH反应者比例与CTTH无反应者比例）。
在CM组中，76.1%（54 /71）的患者对BoNTA有反应，其中68.5%（37/54）的患者头痛主要为单侧，其余31.5%（17/54）的患者头痛主要为双侧（与CM无反应者相比，两者P均<0.01）。在23.9%（17/71）的CM无反应者中，76.5%（13/17）报告头痛主要为双侧，其余23.5%（4/17）的头痛为单侧。在CM反应者组中，81.5%（44/54）有临床可检测到的头皮异常性疼痛，而61.1%（33/54）存在颅周肌肉压痛（与CM无反应者相比，两者P均<0.01）。CM无反应者中头皮异常性疼痛和颅周肌肉压痛的发生率分别为11.8%（2/17）和17.6%（3/17）。在CTTH组中，所有患者（100%，11/11）均有双侧头痛，36.4%（4/11）的患者对BoNTA有反应。所有这些CTTH反应者（100%，4/4）均有颅周肌肉压痛（与CTTH无反应者相比，P<0.05）。CTTH无反应者均无颅周肌肉压痛。未报告具有临床意义的严重不良事件（AE）。11例患者报告了轻度AE，如持续1 - 9天的注射部位疼痛。1例患者有短暂性眉下垂。
CM患者对BoNTA有反应的比例高于CTTH患者。主要为单侧位置的头痛、头皮异常性疼痛的存在以及颅周肌肉压痛似乎是CM患者对BoNTA反应的预测因素，而在CTTH中，颅周肌肉压痛可能是反应的预测因素。
