Objective: To report the efficacy of bilateral subthalamic nucleus (STN) Deep Brain Stimulation (DBS) in two siblings with Juvenile Parkinson’s Disease (JP) due to homozygous mutations in the PTPA gene.

Background: DBS may be effective for genetic forms of Parkinson’s disease (PD) with outcome influenced, amongst others, by the specific gene that is affected.(1) Mutations in the PTPA gene have been implicated as a novel cause of PD characterized by JP  with intellectual disability (ID).(2)

Method: We present the long-term motor and non-motor outcomes of bilateral STN  DBS in two siblings with JP due to homozygous PTPA gene mutations.

Results: Patient 1 (P1) presented at 11 years of age with ID, right-sided levodopa- responsive resting tremor and ankle dystonia. After treatment with levodopa for 11 years, he underwent bilateral STN DBS for intolerable levodopa-induced motor fluctuations, peak dose dyskinesia and dopamine agonist related impulse control disorder (ICD).

Preoperatively P1 was on best medical therapy at a levodopa equivalent daily dose (LEDD) of 2000mg /day. 11 years postoperatively P1 has a LEDD of 1050mg/day and shows sustained improvement in best on state with his United Parkinson’s Disease Rating Scale (UPDRS) improving from 52, medication and stimulation off, to 22 in best on state. His ICD resolved fully.

Patient 2 (P2), the sister of P1, presented at 13 years with milder ID, and levodopa-responsive tremor. P2 developed freezing of gait and right ankle dystonia with levodopa-induced motor complications and underwent bilateral STN DBS at 15 years of age. P2 also showed a marked and sustained reduction in LEDD with her presurgical LEDD being 1448mg/day compared to 950mg/day 13 years post DBS surgery. P2 shows a greater improvement in UPDRS: her medication and stimulation off UPRDS improves from 58 to 14 with medication and stimulation on.

Neither P1 nor P2 showed any significant cognitive decline or notable side-effects after undergoing DBS surgery.

Conclusion: Bilateral STN DBS may be an effective treatment option for PD caused by mutations in the PTPA gene with these case studies demonstrating sustained benefits without serious side effects of surgery or STN stimulation.

References: 1. Asimakidou E, Xiromerisiou G, Sidiropoulos C. Motor and Non-motor Outcomes of Deep Brain Stimulation across the Genetic Panorama of Parkinson’s Disease: A Multi-Scale Meta-Analysis. Movement Disorders Clinical Practice..
2. Fevga C, Tesson C, Carreras Mascaro A, Courtin T, van Coller R, Sakka S, et al. PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability. Brain. 2023;146(4):1496-510.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/bilateral-subthalamic-nucleus-deep-brain-stimulation-as-effective-and-sustained-therapy-in-juvenile-parkinsons-disease-due-to-ptpa-gene-mutations/