Oculomotor abnormalities indicate early executive dysfunction in prodromal X-linked dystonia-parkinsonism (XDP)

Renana Mertin, Cid Diesta, Norbert Brüggemann, Raymond L. Rosales, Henrike Hanssen, Ana Westenberger, Julia Steinhardt, Marcus Heldmann, Hans T.S. Manalo, Jean Q. Oropilla, Christine Klein, Christoph Helmchen, Andreas Sprenger*

*Corresponding author for this work
2 Citations (Scopus)


Background: X-Linked dystonia-parkinsonism (XDP) is a movement disorder characterized by the presence of both dystonia and parkinsonism with one or the other more prominent in the initial stages and later on manifesting with more parkinsonian features towards the latter part of the disease. XDP patients show oculomotor abnormalities indicating prefrontal and striatal impairment. This study investigated oculomotor behavior in non-manifesting mutation carriers (NMC). We hypothesized that oculomotor disorders occur before the appearance of dystonic or parkinsonian signs. This could help to functionally identify brain regions already affected in the prodromal stage of the disease. Methods: Twenty XDP patients, 13 NMC, and 28 healthy controls (HC) performed different oculomotor tasks typically affected in patients with parkinsonian signs. Results: The error rate for two types of volitional saccades, i.e., anti-saccades and memory-guided saccades, was increased not only in XDP patients but also in NMC compared to HC. However, the increase in error rates of both saccade types were highly correlated in XDP patients only. Hypometria of reflexive saccades was only found in XDP patients. Initial acceleration and maintenance velocity of smooth pursuit eye movements were only impaired in XDP patients. Conclusions: Despite being asymptomatic, NMC already showed some oculomotor deficits reflecting fronto-striatal impairments, typically found in XDP patients. However, NMC did not show saccade hypometria and impaired smooth pursuit as seen in advanced Parkinson’s disease and XDP, suggesting oculomotor state rather than trait signs in these mutation carriers. Neurodegeneration may commence in the striatum and prefrontal cortex, specifically the dorsolateral prefrontal cortex.

Original languageEnglish
JournalJournal of Neurology
Issue number9
Pages (from-to)4262-4275
Number of pages14
Publication statusPublished - 09.2023

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
  • Research Area: Medical Genetics

DFG Research Classification Scheme

  • 206-06 Molecular and Cellular Neurology and Neuropathology
  • 206-07 Clinical Neurology Neurosurgery and Neuroradiology

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