ABSTRACT
OBJECTIVES: Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients. RESULTS: The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients. CONCLUSION: Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia.
Subject(s)
Deep Brain Stimulation , Dystonia , Dystonic Disorders , Heredodegenerative Disorders, Nervous System , Child, Preschool , Female , Humans , Male , Dystonia/genetics , Dystonia/therapy , Dystonic Disorders/genetics , Dystonic Disorders/therapy , Globus Pallidus/physiology , GTP-Binding Protein alpha Subunits, Gi-Go , Treatment Outcome , Infant, Newborn , Infant , ChildABSTRACT
BACKGROUND: To maximize clinical benefit and minimize stimulation-induced side effects, optimising deep brain stimulation (DBS) parameters is paramount. Recent literature suggests a potential benefit of short pulse width DBS (spDBS; ≤40 µs) over conventional pulse width DBS (cDBS; ≥60 µs) in movement disorders. OBJECTIVE: To compare therapeutic window (TW), therapeutic and side effects and energy consumption of spDBS and cDBS in movement disorders. METHODS: We systematically searched Medline, Embase, Cochrane Library and Web of Science. Appropriate paired analyses were performed. RESULTS: Nine Parkinson's disease (PD) (143 patients), 4 essential tremor (ET) (26 patients) and no dystonia studies were included in the meta-analysis. TW defined as therapeutic amplitude range was larger with spDBS vs. cDBS in PD (standardized mean difference (SMD) = -1.04, p < 0.001) and ET (SMD = -0.71, p < 0.001), but the TW in terms of charge per pulse (CPP) did not differ. In PD, no differences were found in therapeutic and side effects (MDS-UPDRS-III, speech and gait, dyskinesia, non-motor symptoms and quality of life). In ET, Fahn-Tolosa-Marin Tremor Rating Scale was lower with spDBS vs. cDBS (SMD = 0.36, p < 0.001). A qualitative analysis suggested fewer stimulation-induced side effects with spDBS. CPP was lower with spDBS vs. cDBS in PD (SMD = 0.79, p < 0.001) and ET (MD = 46.46 nC, p < 0.001), but real-world data on battery longevity are lacking. CONCLUSION: Although spDBS enlarges the TW as a wider amplitude range in both PD and ET, it does not alter TW defined by CPP. The therapeutic efficacy of spDBS is not different from cDBS in PD, but spDBS apparently induces more tremor reduction in ET.
Subject(s)
Deep Brain Stimulation , Essential Tremor , Parkinson Disease , Humans , Parkinson Disease/therapy , Essential Tremor/therapy , Essential Tremor/etiology , Tremor/therapy , Treatment Outcome , Deep Brain Stimulation/adverse effects , Quality of LifeABSTRACT
BACKGROUND: Musician's dystonia is a task-specific focal hand dystonia characterized by involuntary contraction of muscles while playing a musical instrument. Current treatment options are often insufficient. OBSERVATIONS: We present the effects of ventro-oral thalamic deep brain stimulation in a patient with musician's dystonia. The patient was a 67-year-old pianist with musician's dystonia who underwent deep brain stimulation with the ventralis oralis anterior and posterior nuclei of the thalamus as targets. The Tubiana and Chamagne rating scale was used to evaluate the effects of stimulation. The outcome was evaluated independently by four clinicians in a blinded manner at 3 months postoperatively. There was a distinct reduction of symptoms during stimulation. At 15 months postoperatively, the beneficial effect remained. No lasting side effects were observed. LESSONS: Further studies are warranted to evaluate the safety and long-term efficacy of this treatment modality.
