Objective: To report the clinical outcomes of two patients with KMT2B medically refractory dystonia who underwent bilateral deep brain stimulation (DBS) with different targets: subthalamic nucleus (STN) and globus pallidus internus (GPi).

Background: KMT2B-related dystonia (DYT-KMT2B) is a progressive dystonia typically beginning in childhood. It often starts in the lower limbs and evolves into a generalized form, primarily affecting the cervical, cranial, and laryngeal regions (1). DBS application in KMT2B dystonia is an emerging area of research.

Method: Case 1: A 47-year-old man, developed right upper extremity dystonia at age 14 that progressed to generalized dystonia, including jaw and tongue leading to dysarthria. Genetic testing: Gene D KMT2B C.5076+1 G>A heterozygous. He underwent bilateral STN DBS 10 years after the dystonia diagnosis. Post-surgery, upper extremity dystonia and retrocollis nearly resolved, though dysarthria persisted. Side effects included blurred vision, vertigo, and lower extremity bradykinesia. mRS dropped from 4 to 1, improvement sustained for 15 years, off dystonia medications, receives botulinum injection for residual right-hand dystonia.  

Case 2: A 56-year-old woman developed dystonia at age 4 starting in her legs then generalized involving facial muscles, affecting speech and leading to hypophonia and hoarseness. Invitae genetic testing KMT2B C.521dup(p.Thr176Aspfs*8) heterozygous mutation, she underwent bilateral GPi-DBS. Post-surgery she had a microlesion effect with improved speech, mobility and right arm dystonia. mRS dropped from 4 to 2 and sustained at 14 years, speech improved initially but plateaued after 24 months. She receives botulinum injections for right neck laterocollis, remian on Deuterobenzene.

Results: Our case suggests STN as a possible target for KMT2B dystonia. Our follow-up period was > 10 years in both cases and showed sustained improvement. Lack of speech improvements aligns with the literature. Some studies suggest GPi-DBS may worsen laryngeal dystonia.

Conclusion: In conclusion, both STN and GPi DBS appear to be beneficial in managing KMT2B-related dystonia, with significant and long term improvements in motor symptoms. However, factors such as gender, dystonia severity, and mutation type may influence outcomes, though their precise roles remain unclear (2,3).

References: 1. Abela L, Kurian MA. KMT2B-Related Dystonia. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2024 Oct 26]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK493766/
2. KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation – PubMed [Internet]. [cited 2024 Oct 26]. Available from: https://pubmed.ncbi.nlm.nih.gov/33150406/
3. Rajan R, Garg K, Saini A, Radhakrishnan DM, Carecchio M, Bk B, et al. GPi-DBS for KMT2B-Associated Dystonia: Systematic Review and Meta-Analysis. Mov Disord Clin Pract. 2022 Jan;9(1):31–7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-application-of-deep-brain-stimulation-in-kmt2b-dystonia-two-cases-with-different-targets/