Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

Brief Title

Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

Official Title

Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

Brief Summary

      To generate pilot data to investigate the potential to use in vivo iron- and
      neuromelanin-quantification as imaging tools for the diagnostic evaluation of movement
      disorders with predominant dystonia / parkinsonism. To this end we are planning to compare
      the MR imaging neuromelanin and iron-pattern and content in midbrain, striatum and further
      brain structures in clinically similar entities and respective, sex- and age-matched healthy

Detailed Description

      Iron- or Neuromelanin-sensitive MR-imaging has not been consistently applied to the study of
      syndromes presenting with predominant dystonia/parkinsonism yet. We are planning to study the
      following groups, as they can often be very difficult to be distinguished from PD and in
      particular young-onset PD, on clinical grounds only:

        -  Dopa-responsive dystonia (DRD) can present similar to young-onset PD, but carries a
           completely different prognosis, necessitating different treatment requirements due to
           fundamentally different underlying physiology.

        -  Sporadic and Inherited dystonias (i.e. due to TorsinA (DYT1) and other gene mutations)
           often present with dystonia, particularly affecting the leg, which is clinically
           indistinguishable from young-onset PD.

        -  Young-onset PD, i.e. PD presenting with motor symptoms before 45 years of age, caused by
           a familiar gene mutation (PARKIN, Pink, DJ-1, PLA2G6, FBX07, ATP13A2, VPS13C, RAB39B,
           Lubag), often presents with predominant dystonia, particularly with leg-onset.

        -  NBIAs present with dystonia/parkinsonism: while basal ganglia iron accumulation is a
           known hallmark feature of the condition [3], the characteristics of neuromelanin
           regulation are unknown.

        -  Mitochondrial disease presenting with dystonia / parkinsonism (such as for example Leigh
           syndrome due to mutations in the Surf-1 gene or mutations m.3243A>G or POLG) [4]

        -  Respective age- and sex-matched healthy controls This study is designed to produce pilot
           data on these disease entities. By potentially accelerating the diagnostic process and
           identification of disease entities, neurologists might be able to deliver more selective
           and dedicated treatment.

      Furthermore, combining Neuromelanin- and iron-specific imaging will offer the possibility to
      study the condition- specific dynamics of iron homeostasis in these rare conditions.

Study Type


Primary Outcome

neuromelanin content

Secondary Outcome

 neuromelanin association


Sporadic Dystonia


3Tesla MRI

Study Arms / Comparison Groups

 Sporadic Dystonia
Description:  3 Tesla MRI Burke-Fahn-Marsden Dystonia Rating scale MDS-United Parkinsons Disease Rating Scale, Part III Beck Depression Inventory MoCA: Montreal Cognitive Assessment


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Diagnostic Test

Estimated Enrollment


Start Date

July 1, 2018

Completion Date

July 1, 2021

Primary Completion Date

July 1, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  clinical diagnosis of parkinsonism and/or dystonia due to

          -  dopa-responsive dystonia

          -  sporadic or inherited/genetic dystonia

          -  young-onset Parkinson's disease

          -  NBIA

          -  Mitochondrial disease

               -  OR healthy controls

               -  18 to 60 years of age

               -  able to give informed consent

        Exclusion Criteria:

          -  Inability to tolerate 35min in an MRI machine

          -  Participated in a clinical drug trial up to 28 days before inclusion into the present

          -  Contra-indications to 3T MRI on MRI safety grounds, such as presence of
             contra-indicated medical implants, as according to the established routine operating
             procedures for clinical MRI in the Lysholm Department of Neuroradiology at the
             National Hospital for Neurology and Neurosurgery.




18 Years - 60 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Bhatia P Kailash, MD, DM, FRCP, 0203448 8604, [email protected]

Administrative Informations



Organization ID


Secondary IDs

IRAS ID 243171

Responsible Party


Study Sponsor

University College, London

Study Sponsor

Bhatia P Kailash, MD, DM, FRCP, Principal Investigator, UCL, Institute of Neurology, Sobell Department

Verification Date

June 2018