Thesis defense Frederick Meijer (Donders Series 182)

23 June 2015

Promotors: Prof.dr. B. Bloem, prof.dr. B. Goraj, copromotor: Dr. M. Verbeek

Clinical Application of Brain MRI in Parkinsonism: From Basic to Advanced Imaging

Parkinson’s disease is a neurodegenerative disorder with increased prevalence at raising age, and the most frequent cause of parkinsonism. In clinical practice, differentiating Parkinson’s disease from the various forms of neurodegenerative atypical parkinsonism can be difficult, especially in early disease stages. Neurodegenerative atypical parkinsonism includes separate disease entities such multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dementia with Lewy bodies and cortical basal degeneration (CBD). Vascular parkinsonism develops as a result of ischemic cerebrovascular disease, so aetiologically it is classified as secondary parkinsonism. Certain drugs, e.g. neuroleptics, can also cause a hypokinetic-rigid syndrome, but without underlying neurodegenerative pathology. For adequate patient treatment and counseling, it is important to establish the correct diagnosis in early disease stages.

Many types of ancillary investigations have been proposed to improve and accelerate the final clinical diagnosis, but efficient application of ancillary investigations depends on a careful clinical evaluation of each patient. In this regard, brain MR imaging can be employed for various purposes: to assess cerebrovascular damage for the diagnosis of vascular parkinsonism, to exclude rare causes of parkinsonism such as multiple sclerosis or hydrocephalus, or to support the diagnosis of atypical parkinsonism. In the first part of this thesis, the diagnostic challenges in parkinsonism are discussed.

The main objective of the studies presented in this thesis is to evaluate the (added) diagnostic value of brain MR imaging in early stage parkinsonism. The current state of literature concerning brain MR imaging in Parkinson’s disease and neurodegenerative atypical parkinsonism is discussed, both for conventional and advanced MR imaging sequences. Next, the diagnostic value of brain MR imaging in the diagnostic work-up of early stage parkinsonism is evaluated, both for a conventional MR protocol performed at 1 or 1.5 Tesla magnetic field strength, and for a standardized 3 Tesla MR scanning protocol extended with a Susceptibility Weighted Imaging (SWI) and Diffusion Tensor Imaging (DTI) sequence. These studies are part of two larger prospective observational clinical cohort studies.

Brain MR imaging proves to be of added value for the diagnostic work-up of early stage parkinsonism, mainly when there is uncertainty about the clinical diagnosis. To further enhance the diagnostic yield, an optimized MR imaging scanning protocol is advised, which includes a T2* or SWI sequence. We demonstrate that severe hypo-intensity of the putamen on SWI is indicative of MSA-P, and this improves the diagnostic accuracy of brain MRI. High-resolution SWI could possibly provide a new diagnostic marker specific for Parkinson’s disease, though further research is needed to evaluate whether the ‘swallow tail sign’ is of added value in the diagnostic work-up of early stage parkinsonism. Clinical application of quantitative DTI is more complex, as it requires dedicated post-processing, and quantitative measures are dependent on the scanning parameters and magnetic field strength used. It remains to be determined how DTI should be optimally applied to evaluate an individual patient, and whether this technique improves the diagnostic accuracy of brain MRI.