Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study

S. Zittel; J. Kroeger; J. P M van der Vegt; H. R. Siebner; N. Brüggemann; A. Ramirez; M. I. Behrens; C. Gerloff; T. Bäumer; C. Klein; A. Münchau

doi:10.1016/j.parkreldis.2011.10.020

Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study

S. Zittel^*, J. Kroeger, J. P M van der Vegt, H. R. Siebner, N. Brüggemann, A. Ramirez, M. I. Behrens, C. Gerloff, T. Bäumer, C. Klein, A. Münchau

^*Corresponding author for this work

8 Citations (Scopus)

Abstract

Objective: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS).

Methods: Five members of a Chilean family with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions.

Results: CSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC.

Conclusion: A compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical inhibition. In addition, some aspects of interhemispheric inhibition are increased in the presence of a single ATP13A2 mutation.

Original language	English
Journal	Parkinsonism and Related Disorders
Volume	18
Issue number	5
Pages (from-to)	590-594
Number of pages	5
ISSN	1353-8020
DOIs	https://doi.org/10.1016/j.parkreldis.2011.10.020
Publication status	Published - 01.06.2012

Funding

Dr. Zittel has received research support by Merz Pharmaceuticals. Dr. Kroeger and Dr. van der Vegt report no disclosures. Hartwig Siebner received funding for research from the Danish Research Council for Health and Disease (Grant 271-08-0669 , Grant 09-072163 ), the Lundbeck Foundation (Grant R48 A4846 and Grant of excellence R59 A5399 ) and The John and Birthe Meyer Foundation . Dr. Brüggemann is supported by intramural funding of the University of Lübeck ( E17-2009 ). Dr. Ramirez reports no disclosures. Dr. Behrens is funded by Fondecyt Chile Grant 1080569 , 1100165 and Fondap 15010006 . Dr. Gerloff was supported by advisory Boards of Boehringer Ingelheim and Silk Road Medical , and by grants from the DFG ( Ge 844/2-1 , Ge 844/4-1 ), the Bundesministerium für Bildung und Forschung (BMBF competence net stroke, BMBF Multicare), and UKE intramural grants. Dr. Bäumer has received research support by Merz Pharmaceuticals. Dr. Klein has received honoraria for speaking at the Annual Meeting of the American Academy of Neurology and for speaking at international conferences by GSK and Orion Pharma. Dr. Klein is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. She is funded by the Volkswagen Foundation and the Deutsche Forschungsgemeinschaft. Dr. Münchau is supported by the Deutsche Forschungsgemeinschaft ( MU1692/2-2 ). He received research support and honoraria for lectures by Pharm Allergan, Ipsen, Merz Pharmaceuticals. He is supported by the Dystonia Medical Research Foundation (USA) , the Tourette syndrome Association (Germany) and N.E.MO., charity supporting the research of paediatric movement disorders. Appendix

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SDG 3 Good Health and Well-being
SDG 10 Reduced Inequalities

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Zittel, S., Kroeger, J., van der Vegt, J. P. M., Siebner, H. R., Brüggemann, N., Ramirez, A., Behrens, M. I., Gerloff, C., Bäumer, T., Klein, C., & Münchau, A. (2012). Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study. Parkinsonism and Related Disorders, 18(5), 590-594. https://doi.org/10.1016/j.parkreldis.2011.10.020

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title = "Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study",

abstract = "Objective: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). Methods: Five members of a Chilean family with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions. Results: CSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC. Conclusion: A compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical inhibition. In addition, some aspects of interhemispheric inhibition are increased in the presence of a single ATP13A2 mutation.",

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AU - Zittel, S.

AU - Kroeger, J.

AU - van der Vegt, J. P M

AU - Siebner, H. R.

AU - Brüggemann, N.

AU - Ramirez, A.

AU - Behrens, M. I.

AU - Gerloff, C.

AU - Bäumer, T.

AU - Klein, C.

AU - Münchau, A.

PY - 2012/6/1

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N2 - Objective: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). Methods: Five members of a Chilean family with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions. Results: CSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC. Conclusion: A compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical inhibition. In addition, some aspects of interhemispheric inhibition are increased in the presence of a single ATP13A2 mutation.

AB - Objective: To describe excitability of motor pathways in Kufor-Rakeb syndrome (PARK9), an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration caused by a mutation in the ATP13A2 gene, using transcranial magnetic stimulation (TMS). Methods: Five members of a Chilean family with an ATP13A2 mutation (one affected mutation carrier (MC) with a compound heterozygous mutation, 4 asymptomatic MC with a single heterozygous mutation) and 11 healthy subjects without mutations were studied. We measured motor evoked potentials (MEP), the contralateral silent period (cSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short latency afferent inhibition (SAI) as markers of intracortical intrahemispheric inhibition/facilitation and the ipsilateral silent period (iSP) and paired-pulse interhemispheric inhibition (IHI) to probe interhemispheric motor interactions. Results: CSP duration was increased in the symptomatic ATP13A2 MC. The iSP measurements revealed increased interhemispheric inhibition in both the compound heterozygous and the heterozygous MC. Conclusion: A compound heterozygous mutation in the ATP13A2 gene is associated with increased intracortical inhibition. In addition, some aspects of interhemispheric inhibition are increased in the presence of a single ATP13A2 mutation.

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Motor pathway excitability in ATP13A2 mutation carriers: A transcranial magnetic stimulation study

Abstract

Funding

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