Successful GPi stimulation in genetic Parkinson’s disease caused by mosaicism of alpha-synuclein gene duplication: first description

Abstract

DBS is an established therapy for advanced PD [1] and has been reported to be efficacious in a few patients with monogenic parkinsonisms such as LRRK2, Parkin, and PINK1 [2][3][4][5][6]. By contrast, knowledge about the outcome of DBS in patients with SNCA mutations is scarce, since only one case has been reported to date [7].We now report the case of a 26-year-old male with Parkinson's disease due to mosaicism of alpha-synuclein duplication, who has successfully undergone GPi-DBS.The patient, who has no family history of PD, developed PD at the age of 18. He initially presented dystonic posturing and tremor in his left foot. Within a few months, this had progressed to micrographia, bradykinesia and resting tremor in his upper left limb. He subsequently developed mild autonomic failure, and mild cognitive decline, as well as behavior disorders (rage episodes, panic attacks, and hallucinations). He initially showed good response to dopamine agonists, but after a short period levodopa was needed to obtain satisfactory motor control. He also developed impulse control disorders secondary to treatment with dopamine agonists, resulting in punding behaviors (e.g., disassembling guitars, computers and his car).FISH was conducted using rhodamine-labeled SNCA probes at 4q22.1 (BAC RP11-614o7, 151 kb) and 4q21.3 [BAC-RP11-711j3, 192 kb (control)]. Results indicated few or no rearrangements (i.e., B4 FISH probe signals in [20 % of interphase cells scored) [6] in peripheral leucocytes from the patient, but 43 % of oral mucosa cells showed duplication of SNCA gene. No exon dosage rearrangements were detected in SNCA or other relevant PD genes using MLPA technique. Mutations in PINK1, PARK2, and DJ were not found and were excluded as causes for the patient's symptoms. Further description of the ancestral origin, genetic tests and immunohistochemical findings of this patient can be found in Perandones et al. [8].As he rapidly showed disabling motor fluctuations and severe peak-dose dyskinesias refractory to pharmacological strategies, the patient was proposed for DBS. The target chosen was the globus pallidus internus (GPi) based on the dyskinesias that affected his quality of life and the fact that he already presented mild cognitive impairment as demonstrated in the preoperative neuropsychological examination. A quadripolar brain electrode (model 3387, Medtronic) was implanted stereotactically with microregistration technique in each GPi and fixed with the Stimloc system. Magnetic resonance imaging was performed in stereotactic conditions; the images were processed with WinNeus Ò program to identify coordinates for both GPi. The electrodes were connected to a pulse generator (Activa RC; Medtronic).

Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

“…Five patients were reported in five case reports [46][47][48][49][50] (STN n = 4, GPi n = 1). The motor outcome was favourable for all patients in the short-term but 3/5 patients developed cognitive and/or neuropsychiatric problems a few years after implantation.…”

Good outcome in refractory cervical dystopia with combination of Deep Brain Stimulation on globus pallidus internus nucleus and delayed selective periphery rhizotomy with five years follow up

“…We are currently employing this technique for the treatment of refractory cases in several movement disorders. 8 In the post -operatory assessment we registered a clear improvement in the dystonic signs. Six months later, there was a 69% mean improvement in the BFMDRS total movement score what meant a P<0.031, (Wilcoxin signed rank test).…”

Deep Brain Stimulation for the Treatment of Juvenile Parkinsonism: Case Report

“…In the few cases of JP reported in the literature, the eligibility for DBS has been greatly based on the phenotype of the patients and on their responsiveness to levodopa. [27][28][29] For instance, the treatment of a 14-year-old patient, with several motor fluctuations, using bilateral DBS in the STN, has been described. Satisfactory results were obtained with this treatment for JP, even though he became refractory to levodopa and had complications in less than 5 years.…”

“…The outcome was satisfactory, since the symptoms were controlled. 28 Advanced PD patients, with disease onset 40 years before, have benefited from DBS in the STN, with a decrease in dyskinesia and motor fluctuations. 29,30 In spite of the paucity of controlled trials, in some studies it has been reported that DBS can be a good option for the treatment of JP, because it permits the decrease in the dosage of the medication and improves dyskinesia and on/off periods, as observed in the patient of the present case report.…”