Wing‐Beating Tremor‐like Dyskinesia in a <scp>GBA1</scp> Carrier

Levodopa-induced dyskinesia (LID) is mainly classified into two forms: peak-dose dyskinesia and diphasic dyskinesia,1, 2 the former being mostly choreiform and prominent on the more affected side, while the latter typically appear in the lower limbs bilaterally and often present as dystonia.1 Atypical forms, including ocular, respiratory, and square-wave dyskinesia, have been described,1 but peak-dose LID with a tremor-like presentation has not been reported. This 53-year-old Caucasian man with a 10-year history of PD, was referred to us as he developed during the last year a troublesome “tremor” while holding his right upper limb (RUL) in a particular position as a result of his work as a painter, which was apparently treatment resistant. On examination, repetitive, low-frequency, high-amplitude tremor-like movements of his RUL were evident on holding a posture, especially in the wing-beating position (Video 1A). Given his otherwise controlled parkinsonism with the last Levodopa intake having occurred about 1 h before the examination, we wondered whether these movements could be Levodopa related, but he was unable to identify any temporal pattern. We therefore performed a Levodopa challenge: starting after 60 min from the intake of 150/50 mg Melevodopa/Carbidopa, he developed the tremor-like movements of his RUL, which were not present in the pragmatic OFF condition (Video 1B,C) and were hence interpreted as an atypical presentation of peak dose LID. Amantadine (50 mg tid) was added to his Levodopa treatment (100 mg qid), with resolution of this phenomenon. Collaterally, given the early age at onset, genetic analyses were performed disclosing the heterozygous variant c.1552 T>C (rs1557900457) of GBA1, which is reported to be very rare in Gnomad and classified as a “variant of unknown significance” according to the ACMG criteria. Sanger sequencing with targeted PCR was used to avoid amplifying the pseudo-gene. The GCase activity was found to be normal (eg, 4.9 nmol/h; pathological range <2.5 nmol/h), suggesting no functional impact on the enzymatic activity.2 Optimal PD management relies on careful examination as well as on correct interpretation of patients’ complaints in relation to the timing of pharmacological treatment. In this case, the atypical presentation and the patient's report of the phenomenon as a troublesome “tremor” led the treating physician to increase the dopaminergic stimulation, which was inefficacious. The phenomenology of his peak dose LID was in our view in keeping with low-frequency, high amplitude, repetitive, proximal and position-sensitive dystonic movements, bearing close resemblance with the “wing-beating” tremor reported in other dystonic syndromes.3 Notably, the parkinsonian tremor affecting his upper limbs in the OFF condition was phenomenologically very different and this might have been a clue to suspect a different pathophysiological mechanism, beyond the (missed) temporal pattern of occurrence with the Levodopa intakes. Accurate recognition of this rare phenomenology was crucial to ensure appropriate management. It is unknown whether his GBA1 status is related to this phenomenon. Atypical dyskinesia has been reported in GBA1 patients4 but dystonia is not more frequent in GBA1 carriers than in other genetic forms of early-onset PD.5 (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. C.S.: 1BC; 3A M.R.: 1C; 3B M.P.: 1C; 3B P.B.: 1C; 3B R.E.: 1A; 3B Ethical Compliance Statement: Institutional review board was not required for this work. Written informed consent was obtained from the patient for the publication of his clinical data and videos. Written informed consent was signed by the patient for the genetic analysis and for video collecting. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.” Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report. Author disclosures are available in the Supporting Information. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Data S1.COI_disclosure. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.