title: Successful subthalamic stimulation in genetic Parkinson's disease caused by duplication of the α-synuclein gene.
abstract: The α-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson's disease (PD). Particularly triplication, but also duplication, of the SNCA is associated with early-onset rapidly progressing parkinsonism with increased risk of cognitive impairment. There is no report about the effect and safety of Deep Brain Stimulation (DBS) in carriers of this mutation and, in general, data in patients with genetic parkinsonism are scarce. We report a one-year prospective follow-up of subthalamic nucleus (STN) DBS in a 46-year old female carrier of SNCA duplication who developed PD at the age of 41 years, and rapidly showed disabling motor fluctuations and dyskinesias refractory to pharmacological strategies. One year after surgery there was a clinically relevant improvement in motor features with a reduction of 64% in UPDRS III in "off medication" and a complete abolition of peak dose dyskinesias. Patient did not report procedure-related adverse events following STN-DBS except for stimulation-induced right foot dystonia relieved by modulating stimulation parameters. Postoperative cognitive testing showed a decline in executive functions, mostly verbal fluency and attention shifting, compared with presurgical assessment. STN-DBS is safe and effective in patients with SNCA duplication showing a clinical pattern similar to idiopathic PD. Our case suggests that clinical phenotype rather genotype is the main predictor for DBS outcome.
authors.affiliation: Parkinson Department, IRCCS San Camillo, Venice, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Antonini
authors.forename: Manuela
authors.initials: M
authors.lastname: Pilleri
authors.forename: Angelo
authors.initials: A
authors.lastname: Padoan
authors.forename: Andrea
authors.initials: A
authors.lastname: Landi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ferla
authors.forename: Roberta
authors.initials: R
authors.lastname: Biundo
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Avella
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods*; D003866:Depressive Disorder / Q000209:etiology / Q000523:psychology; D004421:Dystonia / Q000209:etiology; D056344:Executive Function / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D007839:Functional Laterality; D020440:Gene Duplication; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D009483:Neuropsychological Tests; D019635:Neurosurgical Procedures; D010300:Parkinson Disease / Q000235:genetics* / Q000523:psychology / Q000628:therapy*; D020531:Subthalamic Nucleus / Q000502:physiology*; D016896:Treatment Outcome; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D051844:alpha-Synuclein; D007980:Levodopa