Objective: To investigate presynaptic cholinergic functioning in cervical dystonia (CD) by comparing [¹⁸F]-FEOBV binding in patients and controls, as well as exploring correlations with motor and non-motor symptoms.

Background: Cholinergic dysfunction in the striatum of dystonia patients has been proposed as a unifying theme in the pathophysiology of dystonia. Both motor and non-motor symptoms of CD may be the result of cholinergic dysfunction as it plays a role in sensorimotor learning, cognition and mood disorders. Due to recent innovations in the field of positron emission tomography (PET) imaging, it is now possible to investigate regions with high cholinergic innervation in vivo.

Method: This study involved 14 CD patients and 15 controls, with participants undergoing clinical assessment using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), a neuropsychological evaluation cognitive domains, questionnaires on mood disorders and quality of life, and an [¹⁸F]-FEOBV PET scan. Data preprocessing and statistical analyses were conducted to compare [¹⁸F]-FEOBV binding between groups with volume of interest (VOI) and voxel-based analyses. Pearson correlations were performed to explore the relation between [¹⁸F]-FEOBV binding in significant VOIs with motor and non-motor symptoms.

Results: VOI analyses revealed increased  [¹⁸F]-FEOBV binding in the pallidum (p=0.048), cerebellar lobe 4-5 (p=0.045) and cerebellar vermis (p=0.018) of CD patients. However, these differences were not robust after correction for multiple comparisons (corrected α = 0.00156). No significant correlations were found between [¹⁸F]-FEOBV binding and the TWSTRS or cognitive functioning. However, correlations were established between higher [¹⁸F]-FEOBV binding in the cerebellum and both worsened depression (R=0.51, p=0.005) and emotional well-being scores (R=-0.491, p=0.007). Voxel-based analysis showed significant clusters of increased [¹⁸F]-FEOBV binding in the striatum and cerebellar grey matter of CD patients (FDR-corrected, p<0.05).

Conclusion: This study describes a hypercholinergic system in CD that might contribute to its pathophysiology. Additionally, correlations between [¹⁸F]-FEOBV binding and non-motor symptoms provide insight into their underlying mechanisms. These findings support the role of the cholinergic system in CD for both motor and non-motor symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-cholinergic-system-in-cervical-dystonia-an-18f-feobv-pet-study/