Study objectives included testing whether presumed levodopa-unresponsive freezing of gait (FOG) in Parkinson’s disease (PD) actually persists in the presence of adequate dopaminergic dosing and to investigate whether the presence of other parkinsonian features and their responsiveness to therapy varies across patients without FOG (NO-FOG), with levodopa-responsive FOG (OFF-FOG), and with levodopa-unresponsive FOG (ONOFF-FOG). Fifty-five PD patients completed levodopa challenges after >12-h OFF with supratherapeutic doses of dopaminergic medications. Observed responses in FOG, measured with MDS-UPDRS-III during the patient reported full “ON”, were used to classify them as NO-FOG, OFF-FOG, or ONOFF-FOG. Serum levodopa levels were measured. Only those with ≥20% improvement in MDS-UPDRS-III score were included in analyses. Levodopa challenge was sufficient to bring about a full “ON” state with ≥20% improvement in 45 patients. Levodopa-equivalent-dose utilized was 142 ± 56% of patients’ typical morning doses. Overall, 19/45 patients exhibited FOG in the full “ON” state (ONOFF-FOG), 11 were classified as OFF-FOG, and 15 NO-FOG. Linear mixed models revealed a highly significant association between serum levodopa level and total MDS-UPDRS-III score that was similar across groups. The ONOFF-FOG group exhibited significantly higher New-FOG-questionnaire and MDS-UPDRS-II scores compared to the OFF-FOG group. Among MDS-UPDRS-III subdomains significant effects of group (highest in ONOFF-FOG) were identified for other axial parkinsonian features. We found that FOG can persist in the full “ON” state brought about by ample dopaminergic dosing in PD. Other axial measures can also be levodopa-unresponsive among those with ONOFF-FOG only. These data provide evidence that ONOFF-FOG is distinct from responsive freezing.

研究目标包括测试在帕金森病 (PD) 中假定的左旋多巴无反应步态冻结 (FOG) 在存在足够多巴胺能剂量的情况下是否确实持续存在，并调查是否存在其他帕金森病特征及其对治疗的反应是否因无 FOG 的患者而异(NO-FOG)、左旋多巴反应性 FOG (OFF-FOG) 和左旋多巴无反应性 FOG (ONOFF-FOG)。55 名 PD 患者在停用超过 12 小时的多巴胺能药物后完成了左旋多巴激发试验。在患者报告完全“开”期间用 MDS-UPDRS-III 测量的 FOG 中观察到的反应用于将它们分类为 NO-FOG、OFF-FOG 或 ONOFF-FOG。测量血清左旋多巴水平。只有那些 MDS-UPDRS-III 评分改善 ≥ 20% 的人被纳入分析。左旋多巴激发足以使 45 名患者进入完全“开”状态，改善≥20%。使用的左旋多巴等效剂量是患者典型早晨剂量的 142 ± 56%。总体而言，19/45 名患者在完全“开”状态 (ONOFF-FOG) 下表现出 FOG，11 名被归类为 OFF-FOG，15 名被归类为 NO-FOG。线性混合模型显示血清左旋多巴水平与总 MDS-UPDRS-III 评分之间存在高度显着的相关性，且各组间相似。与 OFF-FOG 组相比，ONOFF-FOG 组表现出显着更高的 New-FOG 问卷和 MDS-UPDRS-II 分数。在 MDS-UPDRS-III 子域中，组的显着影响（在 ONOFF-FOG 中最高）被确定为其他轴向帕金森病特征。我们发现 FOG 可以持续处于完全“开启”状态，这是由 PD 中充足的多巴胺能剂量引起的。在仅具有 ONOFF-FOG 的患者中，其他轴向测量也可能对左旋多巴无反应。这些数据提供了 ONOFF-FOG 与响应性冷冻不同的证据。