Objective: Dystonia is a hyperkinetic movement disorder with a complex pathophysiology. The medical treatment includes pharmacological treatment, including botulinum toxin (BoNT), which is considered the first-line therapy for focal and segmental dystonia1. The available clinical treatments promote symptom relief but have limited efficacy and systemic side effects. For refractory symptoms, globus pallidus internus (GPi) or the subthalamic nucleus (STN) deep brain stimulation (DBS) can be indicated.

Background: The current evidence for DBS ranges from class I evidence for isolated generalized dystonia to class IV evidence for some acquired combined dystonia (3). Moreover, the responsiveness varies among the monogenetic causes, with good evidence for DYT-TOR1A (DYT1), DYT-SCGE (DYT11), and DYT-TAF1 (DYT3), moderate results in DYT-THAP1 (DYT6) and poor response in DYT-ATP1A3 (DYT-12). 
The recent DYT16, a monogenetic autosomal recessive dystonia with parkinsonism, was described with a mutation in the PRKRA gene. The clinical phenotype is of a generalized dystonia, typically with involvement of the neck and trunk muscles to a greater extent than then limbs; it has oromandibular and laryngeal dystonia and parkinsonism that is not levodopa-responsive. Patients with DYT-PRKRA also do not respond well to anticholinergics.

Method: Here we describe three patients with DYT-PRKRA with refractory symptoms treated with GPi DBS. The patients were assessed by the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) before and six months after surgery and by the Patient’s Global Impression of Change Scale postoperatively.

Results: The BFMDRS motor subscore improved by 42%(102/58,5) in case 1; 49%(63/32) in case 2, and  40% (35/21) in case 3. In the gait analysis, all patients’ time to complete the walk decreased after DBS. Patients improved specially in gait stability, balance and posture with overall good impression about the treatment. Speech was not affected by stimulation and no adverse effects were reported.

Conclusion: Our series is the first prospective study of GPi DBS response in patients with a PRKRA mutation. Although robust conclusions are limited because of the small number of cases, our observation supports GPi DBS as a potentially treatment option for DYT16.

References: Albanese A et al. EFNS guidelines on diagnosis and treatment of primary dystonias. Eur J Neurol. (2011).
RG, C. et al. Surgical treatment of dystonia. Expert Rev Neurother (2018).
S, T. & KR, K. Pallidal Deep Brain Stimulation for Monogenic Dystonia: The Effect of Gene on Outcome. Front Neurol. (2021).
Camargos, S. et al. DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA. Lancet Neurol. 7, 207–215 (2008).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deep-brain-stimulation-in-generalized-dystonia-caused-by-prkra-mutation/