Genetic Subtypes and Deep Brain Stimulation in Dystonia

Alterman, Ron L.; Filippidis, Aristotelis S.

doi:10.1002/mdc3.12660

Cited by 14 publications

(24 citation statements)

References 46 publications

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“…3,9,14 Primary dystonia patients with different genetic etiologies, such as DYT-TOR1A (DYT1), DYT-THAP (DYT6), and DYT-KMT2B (DYT28) mutations, may show different responses to DBS treatment. 5,6,15 Although variable outcomes were reported in previous studies, Patient D, who had the DYT-THAP mutation and presented with dystonia involving the trunk rather than the orofacial region, showed excellent improvement after a 31-month follow-up. 16 DYT-KMT-2B was reported to have good improvement after GPi DBS, and a similar improvement was also observed in Patient E during the 23-month follow-up.…”

Section: Discussionmentioning

confidence: 85%

“…Many isolated dystonia and some combined dystonia are often caused by genetic disorders, and several candidate genes have been identi ed in different regions of the world, such as torsin family 1 member A (TOR1A, DYT1), thanatos-associated [THAP] domain-containing apoptosis-associated protein 1 (THAP1, DYT6) and lysine methyltransferase 2B (KMT2B, DYT28) mutations, in recent years. 2,5,6 This advancement in diagnosis has led to a more comprehensive evaluation of phenomenology and more appropriate selection of treatment strategies for primary dystonia patients, including deep brain stimulation (DBS). 2,5,6 Currently, there is no cure for dystonia.…”

Section: Introductionmentioning

confidence: 99%

“…2,5,6 This advancement in diagnosis has led to a more comprehensive evaluation of phenomenology and more appropriate selection of treatment strategies for primary dystonia patients, including deep brain stimulation (DBS). 2,5,6 Currently, there is no cure for dystonia. In addition to pharmacological, physical, and botulinum toxin therapies, globus pallidus internus (GPi) DBS has become a major treatment for primary and secondary dystonia when the previously described methods fail to improve patient symptoms.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Outcome of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series

Tai

Chou

Lin

et al. 2021

Preprint

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BACKGROUND Among dystonia patients receiving globus pallidus internus (GPi) deep brain stimulation (DBS), long-term outcomes remain to be established. OBJECTIVE To report the long-term outcome of GPi DBS in a patient cohort with idiopathic and acquired dystonia. METHODS In this long-term follow-up cohort, there were 4 patients with idiopathic dystonia and 2 patients with acquired dystonia. The Burk-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to evaluate 6 consecutive patients preoperatively and at 6 months, 12 months, and the last follow-up. The relationship between etiology and clinical improvement was analyzed. Stimulation parameters were evaluated for similarities and differences among these patients. RESULTS The mean follow-up of our cohort was 65.3 months (median 40.5 months). The average improvement in BFMDRS (mean ± SEM) was 56% ± 7.6, 67% ± 6.8 and 66% ± 9.7 at 6 months, 12 months, and last follow-up, respectively. There was greater improvement during long-term follow-up in the 4 patients with idiopathic dystonia than in the 2 patients with acquired dystonia. The 2 most ventral electrodes (contact 0 and 1) were activated in all 11 leads in this cohort. The average stimulation intensity, pulse width and frequency were 2.0 ± 0.24 mA, 252 ± 43 µs, and 99 ± 6.0 Hz, respectively. CONCLUSION Isolated dystonia, either monogenetic or idiopathic, usually responds better to GPi DBS than does acquired dystonia. Selection of patients by dystonia etiology, accurate placement of DBS leads in GPi targets, and proper stimulation programming are crucial to achieve better long-term outcomes.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-Term Outcome of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series

Tai

Chou

Lin

et al. 2021

Preprint

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“…Chart review for the history of genetic testing as etiology for dystonia was also performed. DBS has been shown to be more effective for certain gene mutations, particularly variants DYT1 gene mutations [ 10 , 13 , 14 ]. Fourteen patients in our cohort underwent preoperative genetic testing for DYT gene mutations.…”

Section: Resultsmentioning

confidence: 99%

Generalized Dystonia Treated With Deep Brain Stimulator: An Institutional Single Surgeon Experience

Ghanchi¹,

Bernstein²,

Taka³

et al. 2020

Cureus

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Introduction Dystonia can cause severe disability when left untreated. Once a patient has exhausted medical management, surgical intervention may be the only treatment option. Although not curative, deep brain stimulation has been shown to be beneficial for patients affected by this condition. Our study sought to review patients undergoing deep brain stimulation for medically refractory dystonia to assess outcomes. Methods Our institution's operative database was reviewed retrospectively for all patients undergoing deep brain stimulator placement over the last six years. These medical records were reviewed for the severity of dystonia preoperatively and followed postoperatively for 24 months, focusing on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients with less than two-year postoperative follow-up were excluded from the study. The patients were further stratified by age into Group A, consisting of patients less than 40 years old, and Group B, patients greater than or equal to 40 years old. Other attributes such as age, sex, age of disease onset, disease duration at the time of surgery, genetic tests for dystonia-related genes, and any complication associated with surgery were also reviewed. Results Four hundred fifty-five operative cases for deep brain stimulator placement were reviewed, and 16 patients met inclusion criteria for the study. The mean age for our patient cohort was 43.75 years, with four males and 12 females. The average time from the age of disease onset to time of surgery was 9.7 years for Group A and 10.8 years for Group B; the overall average was 10.3 years. All patients had globus pallidus interna (GPi) as their surgical target. The first incidence of a statistically significant decrease in BFMDRS score was noted at three months postoperatively (p<0.001) when compared to preoperative values. Fourteen patients in our cohort underwent preoperative genetic testing for DYT gene mutations, out of which four were found to have a mutation. Conclusion Our review of outcomes for primary generalized dystonia at our institution found that deep brain stimulator targeting the GPi is safe and effective. We found an overall 88% response rate with younger patients (< 40-year-old) showing a better response at two years than older patients.

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“…8,9 In addition, patients with different genetic subtypes of dystonia exhibit distinct responses to deep brain stimulation. 10 Patients with DYT1 (TOR1A), DYT3 (TAF1), DYT6 (THAP1), and DYT11 (SGCE ) are considered to be responsive to deep brain stimulation, whereas response is usually poor in those with DYT12 (ATP1A3). These observations indicate a pressing need to expand the knowledge of ethnically relevant genetics in patients with dystonia in diverse populations.…”

mentioning

confidence: 99%

A Clinical and Integrated Genetic Study of Isolated and Combined Dystonia in Taiwan

Wu¹,

Chang²,

Lan³

et al. 2022

The Journal of Molecular Diagnostics

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Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). We observed that a genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P Z 0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3% vs 10.5%; P Q4 Z 0.004). The most common causative genes were SGCE followed by GCH1, TH, CACNA1B, PRRT2, MR1, CIZ1, PLA2G6, and PRKN. Genetic causes were identified from single cases in TOR1A, TUBB4A, THAP1, ATP1A3, ANO3, GNAL, KMT2B, SLC6A3, ADCY5, CYP27A1, PANK2, C19orf12, and SPG11. The whole-genome sequencing analysis identified a novel intragenic deletion in OPHN1 in a multiplex family with X-linked dystonia and intellectual delay. Our findings delineate the genetic architecture and clinical spectrum of dystonia-causative pathogenic variants in an Asian population.

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Genetic Subtypes and Deep Brain Stimulation in Dystonia

Cited by 14 publications

References 46 publications

Long-Term Outcome of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series

Long-Term Outcome of Idiopathic and Acquired Dystonia After Pallidal Deep Brain Stimulation: A Case Series

Generalized Dystonia Treated With Deep Brain Stimulator: An Institutional Single Surgeon Experience

A Clinical and Integrated Genetic Study of Isolated and Combined Dystonia in Taiwan

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