title: The subthalamic microlesion story in Parkinson's disease: electrode insertion-related motor improvement with relative cortico-subcortical hypoactivation in fMRI.
abstract: Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.
authors.affiliation: Dept. of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic. jech@cesnet.cz
authors.forename: Robert
authors.initials: R
authors.lastname: Jech
authors.forename: Karsten
authors.initials: K
authors.lastname: Mueller
authors.forename: Dušan
authors.initials: D
authors.lastname: Urgošík
authors.forename: Tomáš
authors.initials: T
authors.lastname: Sieger
authors.forename: Štefan
authors.initials: Š
authors.lastname: Holiga
authors.forename: Filip
authors.initials: F
authors.lastname: Růžička
authors.forename: Petr
authors.initials: P
authors.lastname: Dušek
authors.forename: Petra
authors.initials: P
authors.lastname: Havránková
authors.forename: Josef
authors.initials: J
authors.lastname: Vymazal
authors.forename: Evžen
authors.initials: E
authors.lastname: Růžička
mesh_terms: D046690:Deep Brain Stimulation / Q000379:methods; D004487:Edema / Q000473:pathology; D004599:Electric Stimulation Therapy / Q000379:methods; D004567:Electrodes, Implanted; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D013788:Thalamus / Q000187:drug effects / Q000473:pathology* / Q000601:surgery
chemical_list: D007980:Levodopa