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Lack of central and peripheral nervous system synuclein pathology in R1441G LRRK2-associated Parkinson’s disease
  1. Dolores Vilas1,2,
  2. Ellen Gelpi3,4,
  3. Iban Aldecoa3,5,
  4. Oriol Grau6,
  5. Roberta Rodriguez-Diehl3,7,
  6. Serge Jaumà8,
  7. María José Martí1,9,10,
  8. Eduard Tolosa1,9,10
  1. 1 Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona, Spain
  2. 2 Movement Disorders Unit, Neurology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
  3. 3 Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Spain
  4. 4 Institute of Neurology, Medical University of Vienna, Vienna, Austria
  5. 5 Pathology Department, Biomedical Diagnostic Center, Hospital Clinic de Barcelona, Barcelona, Spain
  6. 6 Cognitive Disorders Unit, Neurology Service, Hospital Clinic, Barcelona, Spain
  7. 7 Behavioral and Cognitive Neurology Unit, Department of Neurology and LIM 22, University of São Paulo, São Paulo, Brazil
  8. 8 Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Spain
  9. 9 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
  10. 10 Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain
  1. Correspondence to Professor Eduard Tolosa, Parkinson disease and Movement Disorder Unit, Neurology Service, Hospital Clínic de Barcelona, Centro de investigación biomédica en red de enfermedades neurodegenerativas (CIBERNED), Barcelona 08036, Spain; ETOLOSA{at}clinic.cat

https://doi.org/10.1136/jnnp-2018-318473

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    In idiopathic Parkinson’s disease (iPD) abundant alpha-synuclein (αSyn) aggregates are present in the central and peripheral autonomic nervous system (PANS). Detection of αSyn aggregates in the peripheral tissue has been suggested as a potential diagnostic marker of Parkinson’s disease (PD) in early and premotor stages.1

    The neuropathology of LRRK2-associated PD (LRRK2-PD) is unexpectedly heterogeneous.2 In most G2019S mutation carriers αSyn loaded Lewy bodies and neurites can be found in the central nervous system (CNS). Some cases though lack the Lewy-type pathology and may show non-specific nigral degeneration. Prominent tau pathology can also be found. Information on neuropathological findings in cases of PD associated with other LRRK2 mutations is very limited, and we are not aware of reports describing the involvement of the PANS.

    Here we describe postmortem central and peripheral neuropathological findings in a PD patient carrier of the R1441G mutation in the LRRK2 gene.

    Case

    A 67-year-old man presented with gait instability and clumsiness in the right leg. At neurological examination, he had hypomimia, action tremor in the right hand, mild asymmetric bradykinesia and rigidity. He suffered from alcohol-related liver disease, diabetes mellitus and polyneuropathy. He had no hyposmia, depression, constipation, orthostatic hypotension, and urinary or erectile dysfunction. Levodopa was started with a good response. His daughter was diagnosed with PD at the age of 32. Genetic analysis revealed a heterozygous R1441G LRRK2 mutation in both of them. Over the following years the disease progressed slightly. At the age of 69 the …

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    Footnotes

    • Contributors DV conducted the study and wrote the manuscript. EG, OG, RR-D and IA conducted the neuropathological study. SJ and MJM reported the clinical history. ET planned the study, reviewed the manuscript and he is also responsible for the overall content.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Next of kin consent obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.