Svorenova Tatiana, Romito Luigi M, Kaymak Ahmet, Mulroy Eoin, Cif Laura, Moro Elena, Zeuner Kirsten E, Zittel Simone, Petry-Schmelzer Jan Niklas, Gruber Doreen, Centen Liesanne, Albanese Alberto, Ostrozovicova Miriama, Han Vladimir, Magocova Veronika, Knorovsky Kamil, Kollova Aurelia, Garavaglia Barbara, Golfrè-Andreasi Nico, Reale Chiara, Mazzoni Alberto, Zorzi Giovanna, Eleopra Roberto, Levi Vincenzo, Foltynie Thomas, Limousin Patricia, Akram Harith, Zrinzo Ludvic, Magrinelli Francesca, Murphy David, Houlden Henry, Kurian Manju A, Baiata Claudio, Paschen Steffen, Lohmann Katja, Volkmann Jens, Hamel Wolfgang, Barbe Michael T, van Egmond Martje E, Tijssen Maj, Ambro Lubos, Jurkova Veronika, Jech Robert, Havrankova Petra, Winkelmann Juliane, Zech Michael, Skorvanek Matej
Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic.
Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic.
Ann Neurol. 2025 Jun 20. doi: 10.1002/ana.27290.
The objective was to evaluate the effects of deep brain stimulation (DBS) in an international cohort of patients with VPS16-related dystonia.
This observational study collected preoperative and postoperative demographic, clinical, stimulation, genetic, neuroimaging, and neurophysiological data of medically refractory DYT-VPS16 patients with implanted DBS in 10 international centers. Motor symptoms and disability outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale Motor (BFMDRS-M) and Disability (BFMDRS-D) scales. A cut-off threshold for considering response to DBS was set at 25% of BFMDRS-M improvement at the last follow-up (FU) compared to baseline.
The cohort consisted of 26 participants (17 men, 65.4%). Age at dystonia onset and surgery was 17.8 ± 10.9 and 35.3 ± 14.8 years, respectively. At the last FU, 102.5 ± 57.3 months (range, 2-216), the mean BFMDRS-M improvement was 41.6 ± 37.3% (26/26 patients) and 34.8 ± 42.6% for the BFMDRS-D (23/26 patients). Most patients (19/26, 73%) were considered responders. Higher motor improvement was associated with stimulation of the ventroposterior portion of the internal globus pallidus. A significant inverse relationship was observed between improvement in BFMDRS-M at last FU, and the presence of spasticity (p = 0.027) and fixed skeletal deformities (p = 0.001) before surgery. Non-responders had a younger age at disease onset and at implantation, shorter disease duration at DBS surgery, and higher baseline BFMDRS scores.
DBS was an effective treatment for three-quarters of patients with pathogenic VPS16 variants in our cohort. Mean motor improvement was most pronounced at the 1-year FU, but persisted at the last FU despite disease progression. ANN NEUROL 2025.
评估脑深部电刺激（DBS）对一组国际VPS16相关肌张力障碍患者的疗效。
这项观察性研究收集了10个国际中心植入DBS的药物难治性DYT-VPS16患者术前和术后的人口统计学、临床、刺激、基因、神经影像学和神经生理学数据。使用伯克-法恩-马斯登肌张力障碍评定量表运动（BFMDRS-M）和残疾（BFMDRS-D）量表评估运动症状和残疾结局。将末次随访（FU）时BFMDRS-M改善程度相对于基线提高25%作为判断对DBS有反应的截止阈值。
该队列由26名参与者组成（17名男性，占65.4%）。肌张力障碍发病年龄和手术年龄分别为17.8±10.9岁和35.3±14.8岁。在末次随访时，时间为102.5±57.3个月（范围2-216个月），BFMDRS-M平均改善41.6±37.3%（26/26例患者），BFMDRS-D平均改善34.8±42.6%（23/26例患者）。大多数患者（19/26，73%）被视为有反应者。较高的运动改善与刺激苍白球内侧核腹后部有关。末次随访时BFMDRS-M的改善与术前存在痉挛（p=0.027）和固定性骨骼畸形（p=0.001）之间存在显著负相关。无反应者发病年龄和植入时年龄较小，DBS手术时病程较短，基线BFMDRS评分较高。
在我们的队列中，DBS对四分之三携带致病性VPS16变异的患者是一种有效的治疗方法。平均运动改善在1年随访时最为明显，但尽管疾病进展，在末次随访时仍持续存在。《神经病学纪事》2025年。
