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From the Movement Disorder Centre (E.M., E.R., A.E.L., C.K.) and Department of Neurosurgery (A.M.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada; Departments of Neurology (J.V., J.H., G.D.) and Neurosurgery (M.O.P.), Christian-Albrechts-University Kiel, Germany; Institute of Medical Biometry and Statistics (I.R.K.) and Departments of Neurology (S.W., A.H., K.L., A.D., P.S., C.K.) and Human Genetics (S.W., K.L., A.D., P.S., C.K.), University of Lübeck, Germany; Sagol Neuroscience Center and Department of Neurology (S.H.-B.), Chaim Sheba Medical Center, Tel-Hashomer, Israel; Department of Neurology (A.S.), Heinrich-Heine-University, Düsseldorf, Germany; and Department of Stereotaxy and Functional Neurosurgery (J.V.), University of Cologne, Germany.
Address correspondence and reprint requests to Dr. Christine Klein, Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany christine.klein{at}neuro.uni-luebeck.de
Objectives: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT–) patients.
Methods: Eighty patients with disease onset at age 
45 years and bilateral STN-DBS were screened for mutations in the Parkin gene and PINK1 gene and for the recurrent p.G2019S mutation in the LRRK2 gene. The Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) scale were used to compare the on- and off-medication conditions preoperatively and in the off-medication/on-stimulation condition postoperatively.
Results: We identified 12 mutation carriers (11 Parkin [6 with 2 mutated alleles, 5 with 1 mutated allele], 1 homozygous PINK1). There were no clinical differences between the MUT– and MUT+ patients preoperatively, except for more severe H-Y stage and postural and gait scores in the on-medication state in the MUT+ group. During the first year after surgery, MUT– patients showed better clinical improvement (56% motor UPDRS improvement) compared with MUT+ patients (36%). However, in the long-term follow-up (3–6 years), both groups presented with the same degree of clinical improvement (MUT–: 44% vs MUT+: 42%). Although the MUT+ group showed more severe axial signs preoperatively, MUT– patients developed levodopa– and deep brain stimulation–resistant axial signs within the first 3 to 6 years postoperatively, which diminished the initial benefit soon after surgery.
Conclusions: Patients with Parkin or PINK1 mutations benefit from subthalamic nucleus deep brain stimulation. However, the clinical response is not superior to non–mutation carriers and might be limited by more advanced axial motor symptoms at a relatively early disease stage.
Abbreviations: DBS = deep brain stimulation; EOP = early-onset parkinsonism; H-Y = Hoehn and Yahr; LD = levodopa; LEDD = levodopa equivalent daily dose; meds = medication; MUT+ = mutation-positive patients; MUT– = mutation-negative patients; NA = not available; NMF = no mutation found; PD = Parkinson disease; PIGD = postural instability/gait dysfunction; STN-DBS = subthalamic nucleus deep brain stimulation; UPDRS = Unified Parkinson’s Disease Rating Scale.
Supplemental data at www.neurology.org
*These two authors contributed equally to this article.
Supported by a grant from the Volkswagen Foundation.
Disclosure: E.M. and J.V. have received honoraria from Medtronic for lecturing and consulting services.
Received June 11, 2007. Accepted in final form September 17, 2007.
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