Dystonia – neurophysiological and neurotransmitter insights
Dystonia – neurophysiological and neurotransmitter insights
This thesis of Saar Lagerweij focuses on dystonia, a movement disorder characterized by involuntary muscle contractions that result in abnormal movements and/or postures. In addition to motor symptoms, patients often experience non-motor symptoms, including cognitive impairment, depression, and anxiety. Dystonia is considered a network disorder involving dysfunction across multiple interconnected brain regions. A major part of this thesis concentrates on cervical dystonia (CD), the most common subtype, affecting the neck muscles.
The primary treatment for dystonia consists of botulinum toxin injections, which reduce muscle overactivity. However, in a subset of patients this treatment is insufficient, and deep brain stimulation (DBS) can be considered. DBS involves implantation of electrodes in the Globus Pallidus interna (GPi), a structure within the basal ganglia. After implantation, stimulation parameters such as voltage and frequency are adjusted based on clinical response. Objective assessment of treatment effects remains challenging due to the lack of reliable biomarkers.
The main aim of this thesis was to identify objective biomarkers for dystonia. The first part investigates whether electromyography (EMG) can objectively quantify dystonic muscle activity. Abnormalities in the EMG power spectrum and increased intermuscular coherence within the 4–12 Hz frequency band were observed in patients with dystonia. These findings support the hypothesis of an underlying pathological neural “drive,” likely originating in the basal ganglia and measurable across brain regions and muscles.
The second part of the thesis examines the role of the cholinergic neurotransmitter system using PET imaging in patients with cervical dystonia. Increased expression of the vesicular acetylcholine transporter (VAChT) was found in the right cerebellum, along with potential associations with non-motor symptoms such as anxiety, depression, and cognitive complaints. Together, these results highlight the importance of further research into EMG-based measures and the cholinergic system as potential biomarkers to improve diagnosis, monitoring, and treatment optimization in dystonia.