Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

• Conditions: Dystonia, Familial; Parkinson Disease, Juvenile; Neurodegeneration With Brain Iron Accumulation 5; Mitochondrial Diseases; Sporadic Dystonia

• Registration Number: NCT03572114
• Lead Sponsor: University College, London

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 controls.

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 Timeline

• Study First Submitted: 2018-02-08
• Status Verified: 2018-06
• Study First Submitted QC: 2018-06-27
• Last Update Submitted: 2018-06-27
• Study First Posted: 2018-06-28
• Last Update Posted: 2018-06-28
• Study Start: 2018-07-01
• Primary Completion: 2021-07-01
• Study Completion: 2021-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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 study
• 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
neuromelanin content	up to 8 weeks	absolute amount of neuromelanin in midbrain, striatum and other areas of the brain

Secondary Outcome Measures

Name	Time	Method
neuromelanin association	up to 8 weeks	correlate neuromelanin quantification with demographic and clinical details
iron association	up to 8 weeks	correlate neuromelanin quantification with demographic and clinical details
Iron content	up to 8 weeks	absolute amount of iron in midbrain, striatum and other areas of the brain