Kiriakakis V, Bhatia K P, Quinn N P, Marsden C D
University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, UK.
Brain. 1998 Nov;121 ( Pt 11):2053-66. doi: 10.1093/brain/121.11.2053.
The clinical picture, risk factors and natural history of tardive dystonia resulting from dopamine-receptor antagonist (DRA) treatment in 107 patients (57 male and 50 female), seen between 1972 and 1995, are described. The mean age at onset (+/- SD) was 38.3 +/- 13.7 years (range 13-68 years), and the age at last follow-up was 46.3 +/- 15.7 years (range 15-80 years). These patients had received DRAs for schizophrenia (39%), for other psychiatric conditions (51.5%) and for non-psychiatric disorders (9.5%). All classes of neuroleptics used were implicated in producing tardive dystonia, which was found to develop at any time, ranging from 4 days to 23 years after their introduction (median 5, mean 6.2 +/- 5.1 years); there was no 'safe' period. Men were significantly younger than women at onset of dystonia, which developed after shorter exposure in men. At onset, the dystonia was focal in 83% of cases, but progressed over months or years and remained focal in only 17% at the time of maximum severity. The craniocervical region was involved in 87% of cases, and was the most commonly affected site both at onset and at maximum severity. There was a correlation between the site and age of onset; the site of onset ascended from the lower limbs to the face as the mean age of onset increased. Overall, the phenomenology of tardive dystonia was indistinguishable from that of primary (idiopathic) dystonia, although retrocollis and anterocollis, as well as torticollis to the right, were significantly more common in tardive dystonia. It is a very persistent disorder; only 14% of our patients had a remission over a mean follow-up period of 8.5 years. Remission occurred after a mean of 5.2 years from onset (range 1-12 years) and 2.6 years after discontinuation of neuroleptics (range 1 month to 9 years). Discontinuation of neuroleptics increased the chances of remission fourfold. Patients with < or = 10 years on neuroleptics had a five times greater chance of remission than those with > 10 years exposure, suggesting that the pathogenetic changes in tardive dystonia may become irreversible after long-term use of these drugs. None of the numerous treatments tried in these patients, including clozapine and botulinum toxin injections, seemed to relate to overall outcome, but there was a significant negative association between the occurrence of remission and the use of benzodiazepines. Although there were hints of a possible genetic predisposition, the question as to whether patients with tardive dystonia have an underlying vulnerability remains unanswered.
本文描述了1972年至1995年间收治的107例（57例男性，50例女性）因多巴胺受体拮抗剂（DRA）治疗导致迟发性肌张力障碍的临床症状、危险因素及自然病史。发病时的平均年龄（±标准差）为38.3±13.7岁（范围13 - 68岁），最后一次随访时的年龄为46.3±15.7岁（范围15 - 80岁）。这些患者接受DRA治疗的原因包括精神分裂症（39%）、其他精神疾病（51.5%）和非精神疾病（9.5%）。所有使用的抗精神病药物类别均与迟发性肌张力障碍的发生有关，该疾病可在引入药物后的任何时间发生，从4天至23年不等（中位数为5年，平均为6.2±5.1年）；不存在“安全期”。肌张力障碍发病时男性的年龄显著低于女性，且男性在较短暴露时间后即发病。发病时，83%的病例肌张力障碍为局限性，但数月或数年后病情进展，在病情最严重时仅17%仍为局限性。87%的病例累及头颈部区域，且在发病时和病情最严重时都是最常受累的部位。发病部位与发病年龄之间存在相关性；随着平均发病年龄的增加，发病部位从下肢上升至面部。总体而言，迟发性肌张力障碍的临床表现与原发性（特发性）肌张力障碍难以区分，尽管后伸颈和前屈颈以及向右的斜颈在迟发性肌张力障碍中更为常见。这是一种非常持久的疾病；在平均8.5年的随访期内，我们的患者中只有14%病情缓解。缓解发生在发病后平均5.2年（范围1 - 12年）和停用抗精神病药物后2.6年（范围1个月至9年）。停用抗精神病药物使缓解的几率增加了四倍。使用抗精神病药物≤10年的患者缓解几率比暴露时间>10年的患者高五倍，这表明长期使用这些药物后迟发性肌张力障碍的致病变化可能变得不可逆。在这些患者中尝试的众多治疗方法，包括氯氮平和肉毒杆菌毒素注射，似乎都与总体预后无关，但缓解的发生与苯二氮䓬类药物的使用之间存在显著的负相关。尽管有迹象表明可能存在遗传易感性，但迟发性肌张力障碍患者是否存在潜在易感性的问题仍未得到解答。
