Thesis defense Marjolein Aerts (Donders Series 163)

27 July 2014

Promotor: Prof.dr. B. Bloem; copromotors: dr. M.M. Verbeek, dr. R.A.J. Esselink

Improving diagnostic accuracy in parkinsonism

Parkinson’s disease is a neurodegenerative disorder characterized clinically by rigidity, bradykinesia and tremor and is caused by degeneration of the dopamine producing substantia nigra in the brain stem. Many diseases resemble Parkinson’s disease, collectively referred to as atypical parkinsonisms. It is important to distinguish between the different underlying disorders for multiple reasons; for example to provide adequate patient counseling, and disease specific complications but also for research purposes.

The studies described in this thesis investigate several ways to improve this diagnostic accuracy in clinical practice. First, we describe a systematic clinical approach. Second, we evaluate the added value of CSF analysis in several forms of atypical parkinsonism, including analysis of the tau and alpha-synuclein proteins and neurotransmitter metabolites.

In the third part of this thesis, a prospective study evaluating the added value of ancillary investigations (IBZM spect, MRI, CSF analysis and EMG) over purely clinical assessment is presented. In 156 patients with parkinsonism of unknown origin at baseline, we demonstrate that clinical assessment is still leading and that the ancillary investigations do not add to the correct diagnosis.

A thorough clinical evaluation remains of the utmost importance to narrow down the differential diagnosis of parkinsonism, and ancillary investigations should not be used in every patient as part of a standardized work-up. Nonetheless, this is often still the case in daily practice. In this thesis, we have established that this is not a rational approach, as the contribution over and above the clinical diagnosis is low. Moreover, most ancillary investigations are costly, invasive and some are potentially even harmful.