Priolo Tiziana, Lamba Laura Doria, Giribaldi Gaia, De Negri Emanuela, Grosso Paolo, De Grandis Elisa, Veneselli Edvige, Buoncompagni Antonella, Viola Stefania, Alpigiani Maria Giannina, Gandullia Paolo, Calevo Maria G
Children's Neuropsychiatry Operative Unit, Department of Neurosciences, Ophthalmology, and Genetics, IRCCS G. Gaslini Institute, University of Genoa, Largo Gaslini 5, Genoa, Italy.
Pediatr Neurol. 2008 Mar;38(3):196-9. doi: 10.1016/j.pediatrneurol.2007.11.004.
Thalidomide was recently reintroduced to treat several immune-mediated pathologies. Peripheral neuropathy is a significant side effect limiting its clinical use. Our aims include: (1) describing and identifying the incidence of clinical or electrophysiologic peripheral neuropathy in children, (2) determining whether peripheral neuropathy correlates with cumulative dose of thalidomide and with age, and (3) defining its reversibility rate. We studied 13 children manifesting immune-mediated pathologies treated with thalidomide at doses ranging from 25-100 mg/day. Clinical and neurophysiologic evaluation was performed before and after starting treatment. Seven children (53.8%) showed neurophysiologic signs of sensory peripheral axonal polyneuropathy. Five presented associated clinical symptoms, while the other two only presented subclinical, neurophysiologic signs of peripheral neuropathy. We found a significant correlation between the incidence of peripheral neuropathy and thalidomide cumulative dose (P = 0.02). We observed a lower incidence of peripheral neuropathy at a cumulative dose <20 gm, and a correlation with age (P < 0.01). The clinical and electrophysiologic recovery rate was 40%, and clinical improvement alone was observed in another 40%. Thalidomide induces dose-dependent and age-dependent peripheral neuropathy at a significant frequency in childhood (53.8%). In our experience a cumulative dosage at >20 gm and long-term administration for >10 months seem to increase the risk of peripheral neuropathy. We propose clinical and neurophysiologic follow-up every 3 months to identify and monitor possible side effects.
沙利度胺最近被重新用于治疗多种免疫介导的疾病。周围神经病变是限制其临床应用的一个重要副作用。我们的目标包括:(1)描述和确定儿童临床或电生理周围神经病变的发生率,(2)确定周围神经病变是否与沙利度胺的累积剂量和年龄相关,以及(3)确定其可逆率。我们研究了13名患有免疫介导疾病且接受沙利度胺治疗的儿童,剂量范围为每天25 - 100毫克。在开始治疗前后进行了临床和神经生理学评估。7名儿童(53.8%)表现出感觉性周围轴索性多神经病的神经生理学体征。5名儿童伴有相关临床症状,而另外两名仅表现出亚临床的周围神经病变神经生理学体征。我们发现周围神经病变的发生率与沙利度胺累积剂量之间存在显著相关性(P = 0.02)。我们观察到累积剂量<20克时周围神经病变的发生率较低,且与年龄相关(P < 0.01)。临床和电生理恢复率为40%,另外4名儿童仅观察到临床改善。沙利度胺在儿童期以较高频率(53.8%)诱发剂量依赖性和年龄依赖性周围神经病变。根据我们的经验,累积剂量>20克且长期给药>10个月似乎会增加周围神经病变的风险。我们建议每3个月进行一次临床和神经生理学随访,以识别和监测可能的副作用。