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Severe Dyskinesia After Administration of SARS-CoV2 mRNA Vaccine in Parkinson's Disease
Movement Disorders ( IF 8.6 ) Pub Date : 2021-08-09 , DOI: 10.1002/mds.28772
Roberto Erro 1 , Antonio Riccardo Buonomo 2 , Paolo Barone 1 , Maria Teresa Pellecchia 1
Affiliation  

Parkinson's disease (PD) patients might be particularly vulnerable to SARS-CoV-2 infection.1 As approved vaccines are not known/expected to interact with the neurodegenerative process and pharmacological treatment, the Movement Disorder Society released a statement to highly recommend vaccination in PD.2

We report on 2 patients, who developed severe dyskinesia after receiving the BNT162b2 (Pfizer/BioNTech) mRNA vaccine. The first patient is a 61-year-old, nondemented lady, with a 11-year history of PD. Her motor conditions were well controlled with no dyskinesia with 125/31.25/200 mg levodopa/carbidopa/entacapone sex.d. plus a 200-mg prolonged-release (PR) formulation at night. In June 2021, about 6 hours after her first vaccine dose she developed severe, continuous, generalized dyskinesia without fever and/or confusion. The treatment dose was reduced to 100/25/200-mg levodopa/carbidopa/entacapone sex.d. with minimal benefit and subsequently to 75/18.75/200-mg levodopa/carbidopa/entacapone sex.d. resulting in the disappearance of dyskinesia and the reemergence of wearing-off. Nonetheless, she deemed this status was preferable and is currently on this regimen after almost 3 weeks after her vaccination. The second patient is a 79-year-old, nondemented lady, with a 5-year history of PD. She had mild wearing-off and occasional slight peak-dose dyskinesia but was fully independent with a stable treatment of 100/25-mg levodopa/carbidopa tid plus a 200-mg PR formulation at night. In June 2021, the day after her second vaccine dose, she developed fever (38°C), confusion, delusions, and continuous severe dyskinesia for 3 days. Laboratory tests revealed an increased D-dimer level (3228 ng/mL). She was treated with paracetamol, and her levodopa was reduced to 350 mg daily. After 2 weeks, she was afebrile, but mild confusion and dyskinesia that are more severe than her baseline persist.

The reasons whereby these patients developed severe dyskinesia, and in one patient delirium, are not clear, but they might have been triggered by systemic inflammatory response.3 Innate immune response following mRNA vaccination is critical for the initiation of adaptive immunity, but there are no available data in the context of SARS-CoV-2 mRNA vaccines. It has been suggested that antigen-presenting cells stimulate the secretion of type I interferons and other inflammatory cytokines4 and this might have increased the permeability of blood–brain barrier and drug availability, thus causing severe dyskinesia. Beyond this, the systemic response might have triggered and/or fostered striatal glia-mediated inflammatory processes, which have been construed to contribute to the genesis of levodopa-induced dyskinesia.5, 6

We acknowledge that many other patients we care have not developed similar reactions. Moreover, these two patients manifested severe dyskinesia following either the first or the second vaccine dose. This highlights that there is a variability in the response triggered by the vaccine that might likely depend on individual immunological profiles. Although future research should identify individual markers of such and other reactions, clinicians should be aware of this possibility and monitor their patients after they receive their vaccination.



中文翻译:

帕金森病患者注射 SARS-CoV2 mRNA 疫苗后的严重运动障碍

帕金森病 (PD) 患者可能特别容易受到 SARS-CoV-2 感染。1由于不知道/预期已批准的疫苗会与神经退行性疾病和药物治疗相互作用,因此运动障碍协会发布了一份声明,强烈推荐在 PD 中接种疫苗。2

我们报告了 2 名在接受 BNT162b2(辉瑞/BioNTech)mRNA 疫苗后出现严重运动障碍的患者。第一位患者是一位 61 岁的非痴呆女士,有 11 年的 PD 病史。她的运动条件以及与125 / 31.25 / 200毫克左旋多巴/卡比多巴/恩他卡朋无运动障碍控制sex.d。加上夜间 200 毫克缓释 (PR) 制剂。2021 年 6 月,在她第一次接种疫苗后约 6 小时,她出现了严重的、持续的、全身性运动障碍,但没有发烧和/或意识模糊。治疗剂量减少到 100/25/200-mg 左旋多巴/卡比多巴/恩他卡朋。获益最小,随后达到 75/18.75/200-mg 左旋多巴/卡比多巴/恩他卡朋性。d. 导致运动障碍消失和消退重新出现。尽管如此,她认为这种状态更可取,并且在她接种疫苗近 3 周后目前正在采用这种方案。第二位患者是一位 79 岁的非痴呆女士,有 5 年的 PD 病史。她有轻微的消退和偶尔的轻微峰值剂量运动障碍,但完全独立于 100/25-mg 左旋多巴/卡比多巴 tid 和 200-mg PR 制剂在晚上的稳定治疗。2021 年 6 月,也就是她第二次接种疫苗的第二天,她出现发烧 (38°C)、意识模糊、妄想和连续 3 天的严重运动障碍。实验室测试显示 D-二聚体水平增加 (3228 ng/mL)。她接受了扑热息痛治疗,她的左旋多巴减少到每天 350 毫克。两周后,她不发烧了,

这些患者出现严重运动障碍以及一名患者出现谵妄的原因尚不清楚,但可能是由全身炎症反应引发的。3 mRNA 疫苗接种后的先天免疫反应对于适应性免疫的启动至关重要,但没有关于 SARS-CoV-2 mRNA 疫苗的可用数据。有人提出抗原呈递细胞刺激 I 型干扰素和其他炎性细胞因子的分泌4这可能增加了血脑屏障的通透性和药物可用性,从而导致严重的运动障碍。除此之外,全身反应可能已触发和/或促进纹状体神经胶质介导的炎症过程,这已被解释为有助于左旋多巴引起的运动障碍的发生。5、6

我们承认,我们照顾的许多其他患者没有出现类似的反应。此外,这两名患者在接种第一剂或第二剂疫苗后表现出严重的运动障碍。这突出表明疫苗引发的反应存在变异性,这可能取决于个体免疫学特征。尽管未来的研究应确定此类反应和其他反应的个体标志物,但临床医生应意识到这种可能性,并在患者接受疫苗接种后对其进行监测。

更新日期:2021-10-18
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