Category: Parkinson's Disease: Genetics
Objective: We present a case with a paradoxical gait response to levodopa in Parkin gene-related early-onset Parkinson’s Disease.
Background: Parkin (PRKN) mutations are the predominant cause of autosomal recessive Parkinson’s disease, responsible for almost half of PD cases with onset before 40 years old.1 These patients respond well to levodopa, dopamine agonists, and anticholinergics.2
Method: A 26-year-old unmarried Chinese male, born to non-consanguineous parents, presented with a 3-year history of gait instability. He specifically complained of tightness of lower limbs during walking, especially on the right. His gait was dystonic with prominent right knee flexion, ankle plantar flexion, and foot inversion with toes posturing and flexion. However, over one year, he developed mild bradykinesia in both upper and lower limbs, more marked on the left, and mild postural tremors in both hands. MDS-UPDRS motor part III score was 15. Genetic analysis revealed heterozygous PRKN mutations, with a missense pathogenic mutation in exon 7 (c.850G>C (p. Gly284Arg) and a deletion mutation in exon 3 (241bp), confirming the diagnosis of Parkin gene-related EOPD.
Results: The patient had improvement in bradykinesia and rigidity on 300mg daily of levodopa (UPDRS Motor part III was 9). However, his gait worsened with bilateral hip flexion and abduction (left > right), flexed knees, ankle inversion, and plantar flexion rebound during the stance phase on the left foot and reduced arm swing bilaterally. Dystonic gait persisted throughout the day and worsened during the ON state, with no diphasic dyskinesia or early morning dystonia. The addition of benzhexol and pramipexole did not result in any improvement. Finally, the discontinuation of levodopa improved his gait. Further administration of amantadine with gradual escalation to 300 mg/day, led to moderate response in his dystonic gait.
Conclusion: This case shows that low-dose levodopa worsened gait in PRKN-related PD. Our patient did not respond to a well-established response to anticholinergic treatment, particularly in PRKN patients who did not respond to levodopa or dopamine agonists.3-5 Instead, he showed a moderate response to amantadine. This challenges the conventional understanding of treatment responses in Parkin gene mutation patients and highlights the need for further research on this rare subtype of PD.
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Over L, Brüggemann N, Lohmann K. Therapies for Genetic Forms of Parkinson’s Disease: Systematic Literature Review. J Neuromuscul Dis. 2021;8(3):341-356. doi:10.3233/JND-200598
Khan NL, Graham E, Critchley P, et al. Parkin disease: a phenotypic study of a large case series. Brain. 2003;126(Pt 6):1279-1292. doi:10.1093/brain/awg142
Kuroda Y, Mitsui T, Akaike M, Azuma H, Matsumoto T. Homozygous deletion mutation of the parkin gene in patients with atypical parkinsonism. J Neurol Neurosurg Psychiatry. 2001;71(2):231-234. doi:10.1136/jnnp.71.2.231
Yamada H, Momose T, Okada M, Kuroiwa Y. Anticholinergic drugs: response of parkinsonism not responsive to levodopa. J Neurol Neurosurg Psychiatry. 2002;72(1):111-113. doi:10.1136/jnnp.72.1.111
Note:This case has been published in Movement Disorders Clinical practice and cited as follows:
Mehta, A., Naheed, D., Tan, L.C.S. and Neo, S. (2024), Paradoxical Gait Response to Levodopa in Parkin-Gene-Related Early-Onset Parkinson’s Disease: Dopa Worsening Dystonia. Mov Disord Clin Pract, 11: 580-581. https://doi.org/10.1002/mdc3.14024
To cite this abstract in AMA style:
D. Naheed, A. Mehta, S. Neo, L. Tan. A Case of Paradoxical Gait Response to Levodopa in Parkin-Gene-Related Early-Onset Parkinson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/a-case-of-paradoxical-gait-response-to-levodopa-in-parkin-gene-related-early-onset-parkinsons-disease/. Accessed November 23, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-case-of-paradoxical-gait-response-to-levodopa-in-parkin-gene-related-early-onset-parkinsons-disease/