Expanding Phenotype and Clinical Heterogeneity in Patients with Identical Mutation of the Parkin Gene
Expanding Phenotype and Clinical Heterogeneity in Patients with Identical Mutation of the Parkin Gene
复制标题
Parkin 基因相同突变患者的表型扩展和临床异质性
作者：
M. Kunishige;T. Mitsui;Y. Kuroda;S. Yoshida;M. Kosaka;Toshio Matsumoto
183这种损伤可能与突触前过度阻断长期失神经肌肉纤维中的胆碱能连接有关，因此患者的亚临床神经肌肉传递缺陷状态是由于最后一次注射BTX而导致的，这种状态是由选定肌肉中一种长期过量的毒素[9]造成的，安全裕度较低[7]，具有轻微的肌肉炎症特征。伴随的运动神经元疾病因痉挛接受治疗[10]使这些患者面临BTX治疗的风险，但我们的患者不符合运动神经元疾病的任何标准，因此预计患者会出现全身无力。不幸的是，没有进行针对毒素的抗体的剂量。它的兴趣在概念上和实践上主要与无反应的主题相关[11，12]。此外，在我们的患者中，BTX的总剂量和治疗间隔是恒定的，并符合安全规则[13]。除了一过性全身无力之外，BTX治疗的不同罕见并发症在文献中很少报道[7，10，14]：流行性感冒综合征伴低热，可能是由于伴随的未诊断的病毒感染或BTX对热原化合物的更直接影响[15]，以及在BTX治疗开始后3个月内偶尔癫痫发作[15]。便秘等自主神经副作用也很少被描述，还有口干、调节困难和出汗减少；这些症状与BTX血流扩散有关[16]，最近主要由B型应用描述。考虑到风险-收益治疗比率，我们的患者没有使用BTX治疗，因为他在6个月时仍然部分和不完全恢复，尽管他的局灶性痉挛再次明显和严重(Ashworth修正评分：4)；到目前为止还没有检测到进一步的伴随病理。
183 ment underlying the damage can probably be related to an excessive presynaptic blocking of cholinergic junctions in long-term denervated muscle fibers so that the patient’s subclinical defective neuromuscular transmission status was precipitated by the last BTX administration by a sort of long-time toxin overdose [9] in selected muscles and with a low safety margin [7] with mild inflammatory muscular features. Generalized weakness is expected in patients affected by concomitant motor neuron diseases treated for spasticity [10] making these patients at risk of BTX therapy but our patient did not meet any of the motor neuron disease criteria. The dosage of the antibodies against the toxin unfortunately was not performed. Its interest is conceptually and practically relevant mostly in nonresponding subjects [11, 12]. Besides, in our patient the total dosage of BTX and treatment intervals were constant and according to the safety rules [13]. Different unusual complications of BTX therapy apart from transitory generalized weakness [7, 10, 14] are seldom reported in the literature: a flu-like syndrome with low-grade fever that could be due either to concomitant undiagnosed viral infections or to a more direct effect of BTX on pyrogen compounds [15] and occasional seizures within 3 months from the onset of BTX therapy are reported [15]. Autonomic side effects such as constipation are also rarely described as well as a dry mouth, accommodation difficulties, and reduced sweating; these symptoms are related to a BTX bloodstream diffusion [16] and recently described mostly by BTXtype B application [17]. Our patient was not retreated with BTX in consideration of the risk-benefit therapy ratio and because of his still partial and incomplete recovery at 6 months, even though his focal spasticity was again marked and severe (Ashworth modified scale: 4); thus far no further concomitant pathology had been detected.