Pallidal Deep Brain Stimulation Improves HPCA‐Linked (DYT 2) Dystonia

Abstract

Dystonia, characterized by involuntary muscle contractions, often impairs quality of life (QoL) despite conventional treatments like oral medication and botulinum toxin injections. While dystoniarelated genes like TOR1A, THAP1, GCH1, and KMT2B are common, the rare hippocalcin (HPCA)-DYT2 variants present diverse clinical pictures and responses to treatment. [1][2][3][4][5][6][7] The efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) varies across monogenic dystonias, and to date, there are no reports of DBS in patients with HPCA variants. 8-10 Here, we present a patient carrying two HPCA variants who underwent successful bilateral GPi DBS.A 20-year-old male with walking and speech difficulties since age 8 and a history of febrile seizures at ages 18 and 24 months was admitted for treatment. His mental and motor developmental milestones were delayed post-seizures, and at 17, he developed lower limb dystonia, which eventually extended to his upper extremities, trunk, and facial muscles within 2 years. Despite normal neurological examinations in his consanguineous parents, he exhibited jerky generalized dystonia affecting mainly trunk, arms, legs, neck, face, bulbar, and laryngeal muscles, accompanied by mild dysphagia for both solids and liquids. Despite normal cranial MRI, electroencephalography, complete blood cell count, biochemical evaluations, serum and urine copper, ceruloplasmin, and CSF evaluation, HPCA:c.G28del-C; (p.-P10PfsTer80) compound heterozygous mutation was determined in the molecular analysis. 3 Initially responsive to Biperiden (12 mg/day) and botulinum toxin, his condition deteriorated, impairing his activities of daily living (ADL) and necessitating assistance for them (Video 1).At 28 years old, the patient underwent a standard bilateral GPi DBS using 8-contact Vercise standard leads (Boston Scientific Corporation), with the first contact positioned in the ventral GPi (Fig. 1). Following the satisfactory final position of the electrodes, the rechargeable internal pulse generator was implanted subclavically. After DBS surgery, the jerky movements and upper limb dystonia decreased on the third day (Video 2). He was able to eat and drink independently. At the first year after the surgery, he was able to walk and sit independently, and he had no dysphagia, with complete independence in ADL (Video 3). Stimulation parameters were as follows: right GPi, À2 + C, 3.3 mA,