Long term follow-up results of deep brain stimulation of the Globus pallidus interna in pediatric patients with DYT1-positive dystonia

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Highlights

  • DYT1 is a childhood onset dystonia with severe disability in adolescence.

  • GPi DBS has been shown to provide significant improvement in these cases.

  • Our study confirmed positive long-term effects of GPi DBS in DYT1 patients.

  • GPi-DBS induced parkinsonism and cognitive impairment were insignificant in our experience.

Abstract

Objectives

: Primary generalized dystonia (PGD) due to heterozygous torsin 1A (TOR1A) gene mutation (DYT1) is a childhood onset dystonia with rapid deterioration of symptoms, leading to severe disability in adolescence. Globus pallidus interna deep brain stimulation (GPi-DBS) has been shown to provide significant improvement in these cases.

Methods

: This was a retrospective study of TOR1A mutation positive dystonia patients, conducted at a university hospital from 2006 to 2018. Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS) was used to evaluate dystonia severity before and after surgery. Emergence of postsurgical parkinsonian symptoms was evaluated using the Unified Parkinson Disease Rating Scale (UPDRS) part III. Montreal Cognitive Assessment (MOCA) was applied to assess cognitive dysfunction. SPSS version 18 was used for data analysis.

Results

: Eleven patients entered for analysis with an average age of 22.36 (±3.35) years (range: 18–28). Seven patients (63.6 %) were female. Mean follow-up period was 8.72 (±0.87). Difference between baseline and most recent BFM scores was significant (disability: 10.5 ±4.52 versus 2.09 (±3.20), P: 0.001; severity: 48.45 (±17.88) versus 9.36 (±10.47), P<0.001). The mean MOCA and UPDRS III scores after 7–9 years of DBS were 27.18 (±2.99), and 6.09 (±4.15), respectively.

Conclusion

: Our experience confirms that GPi-DBS in pediatric patients with DYT1 dystonia is overall successful, with significant and long-lasting positive effects on motor and cognitive functions. There was no prominent side effect in long-term follow up.

Introduction

Primary generalized dystonia (PGD) due to heterozygous torsin 1A (TOR1A) gene mutation (DYT1) is typically a childhood onset disorder with rapid deterioration of symptoms in adolescence. Current pharmacological treatments are not remarkably effective in slowing symptoms’ progression to severe disability and decline in physical performance [1]. The introduction of deep brain stimulation (DBS) has opened new window to provide improvement in symptoms’ severity and quality of life [2]. DBS of Globus pallidus interna (GPi) in patients with DYT1 dystonia has been widely used with overall promising results [1]. Although it is more than two decades that DBS has been successfully used for dystonia in children, most follow up reports are limited to the first five years of the intervention [3,4,5,6,7,8]. Also a few questions remain unanswered in this field, including variable outcomes, different assessment strategies, as well as the occurrence and type of adverse effects [4,9]. Even eligibility criteria are not very clear when compared with other diseases that have more well-stablished indication protocols for DBS, such as Parkinson’s disease. Finally, motor and cognitive adverse effects [[10], [11], [12], [13], [14]] may pose as significant concern. As such, a few questions regarding long term therapeutic and adverse effect profile of GPi DBS in pediatric dystonia remain unanswered.

We aimed to measure long term follow up (7–10 years post-surgery) and potential adverse effects of GPi DBS in both motor and cognitive domains in children with DYT1 positive dystonia.

Section snippets

Ethics

This is the long-term follow-up results of a previously registered study [14]. The study was approved by the ethical committee of Iran University of Medical Sciences, Tehran, Iran. Written consent forms regarding the procedure, aim of the study and release of the de-identified videos were signed by all patients and their guardians. Helsinki’s declaration was respected in all steps.

Population

Our previously registered prospective cohort study was conducted in movement disorder clinic of Hazrat Rasool

Results

The mean years-of-education for participants was 13.09 (±2.30) years. The mean duration of follow up was 8.72 (±0.87) years.

Table 1 shows the characteristics of the patients. Eleven patients entered the study (4 males, 7 females), with the mean age of 22.36 (±3.35) years; ranging from 18 to 28. The mean age at disease onset, DBS surgery and disease duration before surgery were 8.45 (±1.12), 14.72 (±3.71) and 6.27 (±3.25) years, respectively. The mean duration of follow up after DBS was 8.5 ±

Discussion

This study presents long term effects of bilateral GPi DBS in a relatively large group of pediatric patients with DYT1 generalized dystonia. During this time, benefits (motor and disability scores) and occurrence of adverse effects were assessed. We found that the total BFM score was still significantly decreased after 7–10 years follow up as confirmed by ANOVA test. This score represents an acceptable positive change in functional and daily activities. The plateau mode of the improvement in

Conclusion

GPi DBS in pediatric patients with DYT1 positive generalized dystonia seems to be a successful approach with prosperous long term effects in reducing the severity of dystonia and disability with negligible side effects including on the cognitive abilities.

Funding source

No targeted funding

Financial disclosure

None

CRediT authorship contribution statement

Mona Ramezani Ghamsari: Writing - original draft. Shadi Ghourchian: Formal analysis, Writing - review & editing. Maziar Emamikhah: Writing - review & editing, Software. Mahdi Safdarian: Formal analysis, Writing - review & editing. Gholamali Shahidi: Writing - review & editing. Mansour Parvaresh: Writing - review & editing. Mehdi Moghaddasi: Writing - review & editing. Seyed Amir Hassan Habibi: Writing - review & editing. Renato P. Munhoz: . Mohammad Rohani: Conceptualization, Methodology,

Declaration of Competing Interest

None.

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