Assessment of Graft Effects and Function in Cell Replacement Therapy for Parkinson's Disease

Peter Hagell

    Research output: ThesisDoctoral Thesis (compilation)

    Abstract

    This explorative study aimed to apply, develop, and evaluate assessment methods at various levels in cell replacement therapy for Parkinson’s disease (PD).

    Observed motor effects in five grafted patients support that timed motor tasks and clinical ratings of parkinsonism are able to monitor motor function, but their psychometric properties need further attention.

    Using positron emission tomography in a unilaterally grafted PD patient, dopamine receptor binding of [11C]-raclopride was found upregulated in the non-grafted, but normal in the grafted putamen. Binding reduction was normal in the grafted putamen, but not in other striatal areas, following amphetamine administration. This supports that graft-derived dopamine release can be measured in vivo in PD.

    The Clinical Dyskinesia Rating Scale (CDRS) yielded reliable hyperkinesia ratings, whereas dystonia ratings were reliable within but not between raters. In grafted patients the CDRS showed that grafts can increase dyskinesias, without associated motor improvement and unrelated to the degree of dopaminergic reinnervation. Observations support the value of the CDRS, while reliability problems call for improvements.

    Application of the generic health status questionnaire NHP in grafted patients demonstrated effects beyond motor function, indicating the value of such questionnaires. Psychometric evaluations of the NHP and the PD-specific PDQ-39 showed ambiguities with both, emphasizing the need for further refinements and evaluations, and illustrating the importance of systematic evaluations of outcome measures.

    Although most methods used here require further attention before they can be considered optimal, this study illustrates the value and importance of multi-level assessments of cell replacement therapies in PD.
    Original languageEnglish
    QualificationDoctor
    Awarding Institution
    • Neurology, Lund
    Supervisors/Advisors
    • [unknown], [unknown], Supervisor, External person
    Award date2002 May 4
    Publisher
    ISBN (Print)91-628-5151-9
    Publication statusPublished - 2002

    Bibliographical note

    Defence details

    Date: 2002-05-04
    Time: 10:15
    Place: Segerfalksalen, Wallenberg Neuroscience Center, Lund

    External reviewer(s)

    Name: Hariz, Marwan I.
    Title: Prof
    Affiliation: Norrlands Universitetssjukhus, Umeå, Sweden

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    Article: Hagell P, Schrag A, Piccini P, Jahanshahi M, Brown R, Odin P, Wenning GK, Morrish P, Rehncrona S, Widner H, Brundin P, Rothwell JC, Gustavii B, Björklund A, Brooks DJ, Marsden CD, Quinn NP, Lindvall O. Sequential bilateral transplantation in Parkinson’s disease: Effects of the second graft. Brain 1999; 122: 1121-1132.

    Article: Piccini P, Brooks D, Björklund A, Gunn RN, Grasby PM, Rimoldi O, Brundin P, Hagell P, Rehncrona S, Widner H, Lindvall O. Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient. Nature Neuroscience 1999; 2: 1137-1140.

    Article: Hagell P, Widner H. Clinical rating of dyskinesias in Parkinson’s disease: Use and reliability of a new rating scale. Movement Disorders 1999; 14: 448-455.

    Article: Hagell P, Piccini P, Björklund A, Brundin P, Rehncrona S, Widner H, Crabb L, Pavese N, Oertel WH, Quinn N, Brooks DJ, Lindvall O. Dyskinesias following neural transplantation in Parkinson’s disease. Nature Neuroscience; in press.

    Article: Hagell P, Crabb L, Pogarell O, Schrag A, Widner H, Brooks DJ, Oertel WH, Quinn NP, Lindvall O. Health-related quality of life following bilateral intrastriatal transplantation in Parkinson’s disease. Movement Disorders 2000; 15: 224-229.

    Article: Hagell P, Whalley D, McKenna SP, Lindvall O. Health status measurement in Parkinson’s disease: Feasibility and initial psychometric observations in a Swedish sample. Submitted for publication.

    Subject classification (UKÄ)

    • Neurology

    Free keywords

    • neurophysiology
    • Neurologi
    • neuropsykologi
    • neurofysiologi
    • neuropsychology
    • Neurology
    • measurement
    • psychometrics
    • perceived health
    • dyskinesias
    • assessment
    • striatum
    • positron emission tomography
    • dopamine
    • Parkinson's disease
    • transplantation

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