Objective: A detailed clinical characterization of functional movement disorders (FMD) in dopa-responsive dystonia (DRD) patients.

Background: FMD are one of the most common conditions in neurological practice[1] and also often occur in non-functional neurological disorders[2], e.g., Parkinson’s disease[3]. FMD have not yet been described in DRD. DRD is a monogenic disease predominantly caused by pathogenic variants in the Guanosine triphosphate cyclohydrolase-1 (GCH1) gene. It is characterized by lower-limb dystonia that often generalizes during the disease course, good L-Dopa responsiveness, diurnal fluctuations, and Parkinsonian signs[4].

Method: Nineteen DRD patients (2 male, aged 47±17 years, age at onset 10±13 years) underwent a detailed clinical history and neurological examination by a movement disorders specialist.

Results: All female patients had a classical DRD phenotype with childhood- and lower-limb dystonia onset, diurnal fluctuations, and L-Dopa responsive motor symptoms. Both male patients had an adulthood disease onset. 32% of our cohort (n=6) showed FMD symptoms, which were variable in their severity and phenomenology and characterized by classical clinical signs (e.g., Hoover sign, entrainment). FMD symptoms dominated the current clinical phenotype and the resulting disability. Most frequent FMD symptoms were gait disorders (n=6), weakness (n=4), and tremor (n=2). Five patients were wheelchair-bound due to the FMD gait disorder. FMD symptoms decreased/disappeared under attentional shifting towards an unaffected body region and were unsuccessfully treated by an increase of the dopaminergic medication by general practitioners or neurologists. DRD symptoms (e.g., dystonia and bradykinesia) were L-Dopa responsive, whereas FMD symptoms were not.

Conclusion: FMD appear to be frequent in DRD upon detailed clinical history and neurological examination. In contrast to the L-Dopa responsivity of DRD symptoms, FMD in DRD are not treatable by an increase of the L-Dopa dose. A potential double diagnosis of DRD and FMD should be considered when DRD patients present with L-Dopa non-responsive motor symptoms, which are incongruent to neuroanatomical principles and the DRD phenotype and are inconsistent in their appearance, e.g., due to distractibility[1]. Thus, the clear differentiation of the origin of motor symptoms has strong therapeutic implementations[5].

References: 1. Aybek, S. & Perez, D. L. Diagnosis and management of functional neurological disorder. BMJ o64 (2022) doi:10.1136/bmj.o64.
2. Stone, J. et al. Which neurological diseases are most likely to be associated with “symptoms unexplained by organic disease”. J. Neurol. 259, 33–38 (2012).
3. Wissel, B. D. et al. Functional neurological disorders in Parkinson disease. J. Neurol. Neurosurg. Psychiatry 89, 566–571 (2018).
4. Weissbach, A. et al. Relationship of Genotype, Phenotype, and Treatment in Dopa‐Responsive Dystonia: MDSGENE Review. Mov. Disord. 37, 237–252 (2022).
5. Weissbach A. Metacognitive Therapy and Neuro-Physiotherapy as a Treatment for Functional Movement Disorders – a Randomized, Observer-Blinded Feasibility Trial. clinicaltrials.gov; 2022. Accessed March 14, 2023. https://clinicaltrials.gov/ct2/show/NCT05323344

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-movement-disorders-in-dopa-responsive-dystonia-a-case-series-with-implications-for-diagnosis-and-treatment/