Tsuboi Takashi, Cif Laura, Coubes Philippe, Ostrem Jill L, Romero Danilo A, Miyagi Yasushi, Lozano Andres M, De Vloo Philippe, Haq Ihtsham, Meng Fangang, Sharma Nutan, Ozelius Laurie J, Wagle Shukla Aparna, Cauraugh James H, Foote Kelly D, Okun Michael S
Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, United States.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Front Hum Neurosci. 2020 Jun 25;14:242. doi: 10.3389/fnhum.2020.00242. eCollection 2020.
: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. : In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. : Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, = 0.074; before or after DBS, 91% vs. 47%, = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline. : Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.
揭示多国DYT1肌张力障碍队列中脑深部电刺激（DBS）反应欠佳的临床特征。
在这项多国多中心回顾性研究中，我们分析了DYT1患者的临床数据，这些患者对DBS反应欠佳，定义为与基线相比，最后一次随访时肌张力障碍量表改善<30%。我们使用了一个由112名DYT1患者组成的文献驱动历史队列进行比较。
我们的研究队列中约8%（132例中的11例）对DBS反应欠佳。与历史队列相比，反应欠佳的多国队列发病年龄显著更小（平均7.0岁对8.4岁；P = 0.025），接受DBS时的年龄也更小（平均12.0岁对18.6岁；P = 0.019）。此外，多国队列中头颅受累更为常见（DBS前，64%对45%，P = 0.074；DBS前或后，91%对47%，P = 0.001）。多国队列和历史队列最后一次随访时相对于基线的平均运动改善分别为0%和66%。多国队列的所有11例患者在疾病发作后2.5年内出现肌张力障碍泛化。所有患者术后肌张力障碍均有>30%的改善；然而，肌张力障碍在DBS后6个月至3年开始出现继发性加重。尽管电极植入位置理想、对所有患者进行了多种程控设置试验以及额外的DBS手术，但最后一次随访时的改善仍小于30%。长期随访时的刺激开/关比较表明，尽管未达到超过基线30%改善的阈值，但DBS仍有有益效果。
约8%的患者代表DYT1肌张力障碍更具侵袭性的表型，其特征为发病年龄更小、疾病进展更快和头颅受累，这似乎与对DBS的长期欠佳反应（如继发性加重）有关。这些信息对于临床医生和患者在DBS植入前后的临床决策和患者咨询中可能有用。具有这种表型的患者可能具有不同的神经可塑性、神经遗传学或可能不同的神经生理学。
