NCT03572114

Imaging Neuromelanin and Iron in Dystonia/Parkinsonism

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 80 (estimated)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

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.

Conditions

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

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	3Tesla MRI	1. A previously validated multi-parameter mapping protocol sensitive to neuromelanin and iron content 2. Iron mapping and micro-bleed detection: QSM (quantitative susceptibility mapping), a fully flow-compensated, susceptibility-weighted gradient-echo sequence (5 minutes). 3. 1-mm isotropic anatomical MPRAGE (magnetization-prepared rapid gradient-echo) 4. conventional FLAIR sequence
BEHAVIORAL	Burke-Fahn-Marsden Dystonia Rating scale	internationally standardized examination/quantification of dystonia
BEHAVIORAL	MDS-United Parkinsons Disease Rating Scale, Part III	most recent, internationally standardized examination/quantification of bradykinesia / rigidity according to the Movement Disorder Society
BEHAVIORAL	Beck Depression Inventory	internationally standardized examination to quantify traits of anxiety and depression
BEHAVIORAL	MoCA: Montreal Cognitive Assessment:	internationally standardized examination to quantify cognition, frequently used in studies of dystonia and parkinsonism

Timeline

• Start date: 2018-07-01
• Primary completion: 2021-07-01
• Completion: 2021-07-01
• First posted: 2018-06-28
• Last updated: 2018-06-28