Rossi Malco, Castillo-Torres Sergio A, Merello Marcelo
Servicio de Movimientos Anormales, Departamento de Neurología, Fleni, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Servicio de Movimientos Anormales, Departamento de Neurología, Fleni, Buenos Aires, Argentina.
J Neurol Sci. 2022 Sep 15;440:120354. doi: 10.1016/j.jns.2022.120354. Epub 2022 Jul 25.
Mutations in the glucocerebrosidase (GBA) gene represent the most common genetic risk factor for Parkinson's Disease (PD) and are associated with a more aggressive motor phenotype at late stages. However, the motor response at early stages of disease remains understudied.
Retrospective study of PD patients that underwent next-generation sequencing panel tests for PD-related genes. We extracted demographic data and the MDS-UPDRS III response to an acute levodopa challenge (LDC), the best ON score, and the levodopa equivalent daily dose (LEDD) during the first six months after the LDC and initiation of DRT. We compared the response of GBA-PD patients to that of patients without pathogenic variants or rearrangements in other PD related genes (sporadic PD).
13 GBA-PD and 48 sporadic PD patients were identified. Baseline MDS-UPDRS III score (24.6 ± 9.6 vs. 21.8 ± 9.3. p = 0.4), response to LDC (39.2% ± 7.9% vs. 32.7% ± 13.4%; p = 0.1), best ON score (36.9% ± 39.5% vs. 41.6% ± 20.8%; p = 0.6) and LEDD (188 mg ± 100 mg vs. 261.8 mg ± 164.8 mg; p = 0.2) during the first six months after initiation of DRT were not different between GBA-PD and sporadic PD patients.
At early disease stages of GBA-PD, the motor response to acute levodopa challenge test and the initial response to DRT are similar to that of patients with sporadic PD. Although limited by small sample size, these preliminary findings should be confirmed by future prospective larger studies.
葡萄糖脑苷脂酶（GBA）基因突变是帕金森病（PD）最常见的遗传风险因素，且与晚期更具侵袭性的运动表型相关。然而，疾病早期的运动反应仍未得到充分研究。
对接受PD相关基因二代测序panel检测的PD患者进行回顾性研究。我们提取了人口统计学数据以及运动障碍协会帕金森病统一评分量表第三部分（MDS-UPDRS III）对急性左旋多巴激发试验（LDC）的反应、最佳“开”期评分，以及LDC和开始多巴胺替代治疗（DRT）后前六个月的左旋多巴等效日剂量（LEDD）。我们比较了GBA-PD患者与其他PD相关基因无致病变异或重排的患者（散发性PD）的反应。
共识别出13例GBA-PD患者和48例散发性PD患者。DRT开始后前六个月，GBA-PD患者与散发性PD患者的基线MDS-UPDRS III评分（24.6±9.6对21.8±9.3，p = 0.4）、对LDC的反应（39.2%±7.9%对32.7%±13.4%；p = 0.1）、最佳“开”期评分（36.9%±39.5%对41.6%±20.8%；p = 0.6）和LEDD（188mg±100mg对261.8mg±164.8mg；p = 0.2）并无差异。
在GBA-PD的疾病早期阶段，对急性左旋多巴激发试验（LDC）的运动反应以及对DRT的初始反应与散发性PD患者相似。尽管受样本量小的限制，但这些初步发现应通过未来更大规模的前瞻性研究加以证实。
