Gross motor function outcomes following deep brain stimulation for childhood-onset dystonia: A descriptive report

Tustin, Kylee; Elze, Markus C.; Lumsden, Daniel E; Gimeno, Hortensia; Kaminska, Margaret; Lin, Jean-Pierre

doi:10.1016/j.ejpn.2019.02.005

Cited by 12 publications

(31 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A 2013 metanalysis of pallidal DBS in acquired dystonia that included 19 unblinded studies showed overall im- provements of 23.6% in BFMDRS motor scores and 9.2% in BFMDRS disability scores, 6 with greater improvement seen among younger individuals. More recent studies confirm highly variable and often-disappointing gross motor responses in other etiologies apart from isolated dystonia, 26,27 including acquired, heredodegenerative, and idiopathic dystonia, highlighting the need for alternative brain targets.…”

Section: Discussionmentioning

confidence: 99%

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial

Luciano

Robichaux‐Viehoever

Dodenhoff

et al. 2021

Journal of Neurosurgery: Pediatrics

View full text Add to dashboard Cite

OBJECTIVEThe aim of this study was to evaluate the feasibility and preliminary efficacy and safety of combined bilateral ventralis oralis posterior/ventralis intermedius (Vop/Vim) deep brain stimulation (DBS) for the treatment of acquired dystonia in children and young adults. Pallidal DBS is efficacious for severe, medication-refractory isolated dystonia, providing 50%–60% long-term improvement. Unfortunately, pallidal stimulation response rates in acquired dystonia are modest and unpredictable, with frequent nonresponders. Acquired dystonia, most commonly caused by cerebral palsy, is more common than isolated dystonia in pediatric populations and is more recalcitrant to standard treatments. Given the limitations of pallidal DBS in acquired dystonia, there is a need to explore alternative brain targets. Preliminary evidence has suggested that thalamic stimulation may be efficacious for acquired dystonia.METHODSFour participants, 3 with perinatal brain injuries and 1 with postencephalitic symptomatic dystonia, underwent bilateral Vop/Vim DBS and bimonthly evaluations for 12 months. The primary efficacy outcome was the change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) scores between the baseline and 12-month assessments. Video documentation was used for blinded ratings. Secondary outcomes included evaluation of spasticity (Modified Ashworth Scale score), quality of life (Pediatric Quality of Life Inventory [PedsQL] and modified Unified Parkinson’s Disease Rating Scale Part II [UPDRS-II] scores), and neuropsychological assessments. Adverse events were monitored for safety.RESULTSAll participants tolerated the procedure well, and there were no safety concerns or serious adverse events. There was an average improvement of 21.5% in the BFMDRS motor subscale score, but the improvement was only 1.6% according to the BADS score. Following blinded video review, dystonia severity ratings were even more modest. Secondary outcomes, however, were more encouraging, with the BFMDRS disability subscale score improving by 15.7%, the PedsQL total score by 27%, and the modified UPDRS-II score by 19.3%. Neuropsychological assessment findings were unchanged 1 year after surgery.CONCLUSIONSBilateral thalamic neuromodulation by DBS for severe, medication-refractory acquired dystonia was well tolerated. Primary and secondary outcomes showed highly variable treatment effect sizes comparable to those of pallidal stimulation in this population. As previously described, improvements in quality of life and disability were not reflected in dystonia severity scales, suggesting a need for the development of scales specifically for acquired dystonia.Clinical trial registration no.: NCT03078816 (clinicaltrials.gov)

show abstract

Section: Discussionmentioning

confidence: 99%

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial

Luciano

Robichaux‐Viehoever

Dodenhoff

et al. 2021

Journal of Neurosurgery: Pediatrics

View full text Add to dashboard Cite

show abstract

“…35 DBS is effective in children with DYT1 dystonia due to mutations in the TOR1A gene, 36 DYT6-related disease due to dominant mutation in the THAP1 gene, 37 GNAO1-associated hyperkinesia, 38 and KMT2B-related dystonia, 39 and provides effective symptom palliation in PKAN. 36 The sustained benefits of DBS range from improvement in gross motor function, 35 prevention of life-threatening hyperkinesia events, 38 reduction in dystonia, 36,37,39,40 and even restoration of independent ambulation. 39 Target drugs with unknown mechanism of action Carbamazepine for paroxysmal kinesigenic dyskinesia Paroxysmal kinesigenic dyskinesia (PKD) is one of the most common paroxysmal movement disorders; attacks are typically short (<1min), without loss of consciousness and pain.…”

Section: Caffeine In Adenyl Cyclase 5 Dyskinesiamentioning

confidence: 99%

“…Over time, it is increasingly being used as an early option for a number of monogenic inherited dystonias where DBS is emerging as a highly efficacious treatment modality. 35 DBS is effective in children with DYT1 dystonia due to mutations in the TOR1A gene, 36 DYT6-related disease due to dominant mutation in the THAP1 gene, 37 GNAO1-associated hyperkinesia, 38 and KMT2B-related dystonia, 39 and provides effective symptom palliation in PKAN. 36 The sustained benefits of DBS range from improvement in gross motor function, 35 prevention of life-threatening hyperkinesia events, 38 reduction in dystonia, 36,37,39,40 and even restoration of independent ambulation.…”

Section: Caffeine In Adenyl Cyclase 5 Dyskinesiamentioning

confidence: 99%

“…In paediatrics, DBS was initially considered only in pharmacoresistant cases of childhood dystonia. Over time, it is increasingly being used as an early option for a number of monogenic inherited dystonias where DBS is emerging as a highly efficacious treatment modality 35 . DBS is effective in children with DYT1 dystonia due to mutations in the TOR1A gene, 36 DYT6‐related disease due to dominant mutation in the THAP1 gene, 37 GNAO1 ‐associated hyperkinesia, 38 and KMT2B ‐related dystonia, 39 and provides effective symptom palliation in PKAN 36 .…”

Section: Precision Medicine Approaches For Genetic Childhood Movement Disordersmentioning

confidence: 99%

See 1 more Smart Citation

Precision medicine for genetic childhood movement disorders

Soo

Ferrini

Kurian

2021

Develop Med Child Neuro

View full text Add to dashboard Cite

ABBREVIATIONS AAV Adeno-associated virus ADCY5 Adenylyl cyclase 5 BBB Blood-brain barrier DBS Deep brain stimulation NPC Niemann-Pick disease type C PKAN Pantothenate kinase-associated neurodegeneration PKD Paroxysmal kinesigenic dyskinesiaIncreasingly effective targeted precision medicine is either already available or in development for a number of genetic childhood movement disorders. Patient-centred, personalized approaches include the repurposing of existing treatments for specific conditions and the development of novel therapies that target the underlying genetic defect or disease mechanism. In tandem with these scientific advances, close collaboration between clinicians, researchers, affected families, and stakeholders in the wider community will be key to successfully delivering such precision therapies to children with movement disorders.

show abstract

“…To our knowledge, no systematic way of assessing the outcomes of interventions in dystonia exist using standardised assessments of gross motor function. Preliminary results using GMFM before and after DBS 81 have now been extended to a larger cohort of children and young people and this work will soon be available in the academic literature.…”

Section: 1mentioning

confidence: 99%

The International Classification of Functioning (ICF) to evaluate deep brain stimulation neuromodulation in childhood dystonia-hyperkinesia informs future clinical & research priorities in a multidisciplinary model of care

Gimeno

Lin

2017

European Journal of Paediatric Neurology

Self Cite

View full text Add to dashboard Cite

The multidisciplinary team (MDT) approach illustrates how motor classification systems, assessments and outcome measures currently available have been applied to a national cohort of children and young people with dystonia and other hyperkinetic movement disorders (HMD) particularly with a focus on dyskinetic cerebral palsy (CP). The paper is divided in 3 sections. Firstly, we describe the service model adopted by the Complex Motor Disorders Service (CMDS) at Evelina London Children's Hospital and King's College Hospital (ELCH-KCH) for deep brain stimulation. We describe lessons learnt from available dystonia studies and discuss/propose ways to measure DBS and other dystonia-related intervention outcomes. We aim to report on current available functional outcome measures as well as some impairment-based assessments that can encourage and generate discussion among movement disorders specialists of different backgrounds regarding choice of the most important areas to be measured after DBS and other interventions for dystonia management. Finally, some recommendations for multi-centre collaboration in regards to functional clinical outcomes and research methodologies for dystonia-related interventions are proposed.

show abstract

Gross motor function outcomes following deep brain stimulation for childhood-onset dystonia: A descriptive report

Cited by 12 publications

References 51 publications

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial

Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial

Precision medicine for genetic childhood movement disorders

The International Classification of Functioning (ICF) to evaluate deep brain stimulation neuromodulation in childhood dystonia-hyperkinesia informs future clinical & research priorities in a multidisciplinary model of care

Contact Info

Product

Resources

About