Pallidal Deep Brain Stimulation for KMT2B Related Dystonia in An Indian Patient

Rajan, Roopa; Garg, Kanwaljeet; Saini, Arti; Kumar, Mukesh; Binukumar, B.; Scaria, Vinod; Aggarwal, Rajeev; Gupta, Anu; Vishnu, Venugopalan Y; Garg, Ajay; Singh, Mamta Bhushan; Bhatia, Rohit; Srivastava, Achal K.; Srivastava, M V Padma; Singh, Manmohan

doi:10.4103/aian.aian_1316_20

Cited by 6 publications

(15 citation statements)

References 9 publications

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“…1). [15][16][17][18][21][22][23][24][25][26] We found a total of 42 subjects with DYT-KMT2B who underwent GPi-DBS and had pre-and postoperative outcome data available. Number of patients reported in individual studies ranged from 1 to 17.…”

Section: Resultsmentioning

confidence: 99%

GPi‐DBS for KMT2B‐Associated Dystonia: Systematic Review and Meta‐Analysis

Rajan

Garg

Saini

et al. 2021

Movement Disord Clin Pract

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Background Early evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT‐KMT2B. Objectives We aimed to conduct a systematic review and meta‐analysis to assess outcomes and identify predictors of good outcome following GPi‐DBS in DYT‐KMT2B. Methods We searched MEDLINE, Cochrane and MDS‐abstracts databases using the MeSH terms “KMT2B and DYT28”. We included studies that reported objective outcomes following GPi‐DBS in DYT‐KMT2B. The BFMDRS‐M (Burke‐Fahn‐Marsden Dystonia Rating Scale‐ Movement) total scores pre‐ and post‐surgery were used to quantify outcomes. We calculated pooled effects using a random effects meta‐analysis and used meta‐regression to identify potential effect modifiers. Multiple linear regression using individual patient data was used to identify predictors of good outcome (>50% improvement from baseline on BFMDRS‐M). Results Initial searches screened 132 abstracts of which 34 full‐text articles were identified to be of potential interest. Ten studies reporting 42 individual patients, met the inclusion/exclusion criteria and were included in the final review. The mean age at onset was 6.4 ± 5.7 years and 40% were male. The median follow‐up was 12 months (range: 1–264 months). GPi‐DBS resulted in median BFMDRS‐M improvement of 42.7% (range: −103.5% to 95.9%) postoperatively. Pooled proportion of patients experiencing clinical improvement >50% on BFMDRS‐M was 41% (95% CI: 27%–57%). Male gender [β: 22.6, 95% CI: 8.0–37.3, P = 0.004), and higher pre‐operative BFMDRS‐M score [β: 0.62, 95% CI: 0.36–0.87, P < 0.001) were independently associated with better outcome. Conclusion KMT2B‐associated dystonia responds effectively to pallidal stimulation. The outcome is better in males and those with more severe dystonia at baseline.

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Section: Resultsmentioning

confidence: 99%

GPi‐DBS for KMT2B‐Associated Dystonia: Systematic Review and Meta‐Analysis

Rajan

Garg

Saini

et al. 2021

Movement Disord Clin Pract

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“…Several adult and pediatric patients underwent GPi-DBS due to DYT-THAP1 and DYT-KMT2B. Although the number of pediatric patients was lower, the results prove that bilateral GPi-DBS is a valuable therapeutic option for DYT-THAP1 (8)(9)(10)(11)(12)(13)(14)(15)(16) and DYT-KMT2B, particularly for movement disorders and regaining mobility, but less so for speech issues (5,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) (Supplementary Tables 1, 2). So far, the aforementioned patients presented with severe dystonic postures, majorly impacting their quality of life, as well as those of their families and caregivers.…”

Section: Discussionmentioning

confidence: 94%

“…Further clinical characteristics, such as cognitive disability, psychiatric comorbidities, and dysmorphic features, have been reported in several patients (27-29). Bilateral GPi-DBS has been reported as an efficient therapeutic option, especially for improving movement disorder and regaining independent mobility (5,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). GPi-DBS is sometimes associated with "dramatic" amelioration in gait but more commonly associated with truncal dystonia and scoliosis; it is rarely associated with speech dysfunction in severely affected patients with KMT2B gene mutations prior to DBS (23).…”

Section: Discussionmentioning

confidence: 99%

“…Although it is suggested that DBS should be considered as a treatment approach in pharmacoresistent DYT-THAP1 early in childhood to prevent more severe symptoms, such as disabling motor development and quality of life decline, including emotional and social aspects, the results are missing. Additionally, bilateral GPi-DBS has been reported as a valuable therapeutic option for DYT-KMT2B, especially for regaining motor function and mobility, but less so for speech if significant speech difficulties are developed (5,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

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GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

et al. 2023

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IntroductionDystonia is the third most common pediatric movement disorder and is often difficult to treat. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been demonstrated as a safe and effective treatment for genetic dystonia in adolescents and adults. The results of DBS in children are limited to individual cases or case series, although it has been proven to be an effective procedure in carefully selected pediatric cohorts. The aim of our study was to present the treatment outcome for 7- to 9-year-old pediatric patients with disabling monogenic isolated generalized DYT-THAP1 and DYT-KMT2B dystonia after bilateral GPi-DBS.Patients and resultsWe present three boys aged <10 years; two siblings with disabling generalized DYT-THAP1 dystonia and a boy with monogenic-complex DYT-KMT2B. Dystonia onset occurred between the ages of 3 and 6. Significantly disabled children were mostly dependent on their parents. Pharmacotherapy was inefficient and patients underwent bilateral GPi-DBS. Clinical signs of dystonia improved significantly in the first month after the implantation and continued to maintain improved motor functions, which were found to have improved further at follow-up. These patients were ambulant without support and included in everyday activities. All patients had significantly lower Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) values, indicating >25% improvement over the first 15 months. However, there was a decline in speech and upper limb function, manifesting with bradylalia, bradykinesia, and dysphonia, which decreased after treatment with trihexyphenidyl.ConclusionAlthough reports of patients with monogenic dystonia, particularly DYT-THAP1, treated with DBS are still scarce, DBS should be considered as an efficient treatment approach in children with pharmacoresistent dystonia, especially with generalized monogenic dystonia and to prevent severe and disabling symptoms that reduce the quality of life, including emotional and social aspects. Patients require an individual approach and parents should be properly informed about expectations and possible outcomes, including relapses and impairments, in addition to DBS responsiveness and related improvements. Furthermore, early genetic diagnosis and the provision of appropriate treatments, including DBS, are mandatory for preventing severe neurologic impairments.

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“…DBS is the preferred treatment modality for patients with isolated dystonia without CNS degeneration or insult is because it is reversible. [22][23][24][25][26][27] However, the advantages of DBS in patients with acquired/heredodegenerative dystonia are not definite. 26,28,29 A recent multicenter, single-arm, randomized, double-blind crossover trial on the effect of DBS in pediatric dystonia patients with dyskinetic cerebral palsy concluded that the evidence is insufficient to recommend DBS as routine treatment for these patients.…”

Section: Role Of Pallidotomy In the Era Of Dbsmentioning

confidence: 99%

Bilateral pallidotomy for acquired or heredodegenerative generalized dystonia in children

Garg

Singh

Samala

et al. 2022

Neurosurgical Focus

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OBJECTIVE Dystonias are relatively rare disorders characterized by sustained or intermittent muscle contractions causing abnormal movements or postures. Generalized dystonia is a therapeutic challenge because medications are unable to control dystonia adequately in most patients. These patients may be candidates for surgical therapy. The commonly used surgical procedures in these patients are pallidotomy and deep brain stimulation. Limited studies are available on the role of pallidotomy in children with acquired/heredodegenerative generalized dystonia. The objective of this study was to describe the authors’ experience with bilateral pallidotomy in this group of patients. METHODS The authors retrospectively reviewed all pediatric patients (less than 18 years of age) with acquired/heredodegenerative generalized dystonia who underwent bilateral simultaneous pallidotomy at their center between January 2014 and January 2021. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores before and after surgery were recorded. Complications arising after the procedure were recorded as well. RESULTS Ten patients (8 male and 2 female) with a mean (range) age of 11.1 (5–17) years were included in this study. The mean duration between disease onset and surgical intervention was 3.9 years. Two patients presented in status dystonicus. The mean ± SD (range) preoperative BFMDRS score of the patients without status dystonicus (n = 8) was 80 ± 18.9 (59.5–108). The mean ± SD BFMDRS score at the time of discharge from the hospital after surgery was 58.8 ± 37.9. Three patients had more than 20% change in BFMDRS score at the time of discharge from the hospital. The mean improvement was 25.5% at the end of 1 year. Of 5 surviving patients in the non–status dystonicus group, 3 patients had more than 40% change in BFMDRS score while the other 2 patients developed recurrence at the last follow-up (4.5 years). Status dystonicus abated after bilateral pallidotomy in both patients. Permanent bulbar complications were seen in 2 patients. CONCLUSIONS Bilateral pallidotomy may result in clinically significant improvement in children with acquired/heredodegenerative generalized dystonia, although the benefits should be closely weighed against the risk of irreversible bulbar dysfunction. It is a viable option for children in resource-limited settings.

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Pallidal Deep Brain Stimulation for KMT2B Related Dystonia in An Indian Patient

Abstract: Outcomes of pallidal stimulation in KMT2B dystonia have been infrequently reported prospectively. We report the six-month outcomes of bilateral GPi DBS in an Asian Indian patient with early-onset generalized dystonia associated with a novel heterozygous variant in the KMT2B gene.

Cited by 6 publications

References 9 publications

GPi‐DBS for KMT2B‐Associated Dystonia: Systematic Review and Meta‐Analysis

GPi‐DBS for KMT2B‐Associated Dystonia: Systematic Review and Meta‐Analysis

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

Bilateral pallidotomy for acquired or heredodegenerative generalized dystonia in children

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