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

Parkinsonism Relat Disord. 2012 Jun;18(5):590-4. doi: 10.1016/j.parkreldis.2011.10.020. Epub 2011 Nov 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Chile
  • Efferent Pathways / physiopathology*
  • Electromyography
  • Evoked Potentials, Motor / genetics*
  • Family Health
  • Female
  • Functional Laterality / genetics
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal / physiopathology
  • Mutation / genetics*
  • Neural Inhibition / genetics
  • Parkinsonian Disorders* / genetics
  • Parkinsonian Disorders* / pathology
  • Parkinsonian Disorders* / physiopathology
  • Proton-Translocating ATPases / genetics*
  • Reaction Time / genetics
  • Transcranial Magnetic Stimulation*

Substances

  • ATP13A2 protein, human
  • Proton-Translocating ATPases

Supplementary concepts

  • Kufor-Rakeb syndrome