It is becoming clear that many patients with Parkinson's disease (PD) are experiencing subjective worsening of motor symptoms during the coronavirus disease 2019 (COVID-19) pandemic.¹ However, little evidence using established quantitative scales is available on longitudinal changes in motor symptoms during the pandemic. We therefore evaluated changes in Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS-III), scores during the pandemic.

We included PD patients who continuously visited the Department of Neurology outpatient clinic, The University of Tokyo Hospital, and whose MDS-UPDRS-III (ON) scores and levodopa equivalent daily doses (LEDDs) from May 2019 to October 2020 and those at the last visit before May 2019 were available in their medical records. The observational period was divided into six subperiods of 3 months each. The latter three subperiods were considered part of the pandemic, as the Japanese public began to be urged to stay home from February 2020 after the first infected patient was reported on January 16.² Changes in MDS-UPDRS-III scores from baseline (ΔMDS-UPDRS-III) were averaged for each subperiod. Patients in each subperiod were classified according to the ΔMDS-UPDRS-III values. A ΔMDS-UPDRS-III value between −3 and +4 was considered a minimal clinically important difference (MCID).³ Patients were also categorized according to LEDD changes (increased, maintained, and decreased) during the pre-pandemic and pandemic periods. This study was approved by the ethics board of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo (approval registration number 2339-4).

Forty-four patients were enrolled. The mean age was 69.4 ± 9.1 years, and 22 (50.0%) were female. Thirty-nine (88.6%) showed Hoehn & Yahr stage 1 or 2 at baseline. They had a mean disease duration of 6.7 ± 6.5 years, a mean MDS-UPDRS-III score (ON) of 15.8 ± 9.3, and a mean LEDD of 480.5 ± 277.1 mg. During the pandemic, the mean MDS-UPDRS-III and proportion of patients with worsening motor symptoms (above MCID) were significantly higher than those at baseline (Fig. 1A,B). Furthermore, the number of patients whose LEDDs were increased every 9 months increased significantly after the pandemic outbreak (Fig. 1C).

We found that about 40% of PD patients showed ΔMDS-UPDRS-III above MCID during the pandemic in Tokyo and required increased medication compared with the pre-pandemic period. Because this was a retrospective study with a small sample size without the evaluation of nonmotor symptoms, we cannot comment on the exact reason for this. It is reasonable, however, to assume that people reduced their activity levels despite the lack of legal penalties in Japan for going out,² were staying in a confined space,^{4, 5} and experienced prolonged psychological stress, which may have exacerbated PD motor symptoms by reducing dopaminergic medication efficacy.^{6, 7} Alternatively, the worsening status during the pandemic may be related to disease progression, independent of reduced activity levels or psychological stress.

In conclusion, about 40% of PD patients showed exacerbation of motor symptoms. Careful and continuous evaluation and optimal drug adjustment are important for PD patients during a pandemic.

很明显，在 2019 年冠状病毒病 (COVID-19) 大流行期间，许多帕金森病 (PD) 患者的运动症状出现主观恶化。¹然而，关于大流行期间运动症状的纵向变化，几乎没有证据使用既定的定量尺度。因此，我们评估了大流行期间运动障碍协会统一帕金森病评定量表第三部分 (MDS-UPDRS-III) 分数的变化。

我们纳入了从 2019 年 5 月至 2020 年 10 月连续访问东京大学医院神经内科门诊、MDS-UPDRS-III (ON) 评分和左旋多巴等效日剂量 (LEDD) 的 PD 患者，以及最后2019 年 5 月之前的访问可在他们的病历中找到。观察期分为六个子期，每个子期为 3 个月。后三个阶段被认为是大流行的一部分，因为在 1 月 16^日报告了第一例感染患者后，日本公众从 2020 年 2 月开始被敦促留在家中^。2MDS-UPDRS-III 评分相对于基线的变化 (ΔMDS-UPDRS-III) 对每个子周期进行平均。每个亚时期的患者根据ΔMDS-UPDRS-III值进行分类。-3 和 +4 之间的 ΔMDS-UPDRS-III 值被认为是最小的临床重要差异 (MCID)。³还根据大流行前和大流行期间 LEDD 的变化（增加、维持和减少）对患者进行了分类。本研究获得了东京大学医学研究生院和医学部伦理委员会的批准（批准注册号 2339-4）。

招募了 44 名患者。平均年龄为 69.4 ± 9.1 岁，女性 22 (50.0%)。39 人 (88.6%) 在基线时显示 Hoehn & Yahr 1 期或 2 期。他们的平均病程为 6.7 ± 6.5 年，平均 MDS-UPDRS-III 评分 (ON) 为 15.8 ± 9.3，平均 LEDD 为 480.5 ± 277.1 mg。在大流行期间，平均 MDS-UPDRS-III 和运动症状恶化（MCID 以上）的患者比例显着高于基线（图 1A、B）。此外，大流行爆发后 LEDD 每 9 个月增加一次的患者数量显着增加（图 1C）。

我们发现，在东京大流行期间，大约 40% 的 PD 患者表现出高于 MCID 的 ΔMDS-UPDRS-III，与大流行前相比，需要增加药物治疗。因为这是一项小样本量的回顾性研究，没有评估非运动症状，我们无法评论其确切原因。然而，可以合理地假设，尽管日本没有对外出进行法律处罚，但人们减少了他们的活动水平，²人呆在密闭空间中，^4、5并经历了长时间的心理压力，这可能加剧了 PD 运动症状通过降低多巴胺能药物的疗效。^6、7 或者，大流行期间的恶化状态可能与疾病进展有关，与活动水平降低或心理压力无关。

总之，大约 40% 的 PD 患者表现出运动症状的恶化。在大流行期间，仔细和持续的评估和最佳的药物调整对于 PD 患者很重要。