Quality of life outcomes after deep brain stimulation in dystonia: A systematic review

Abstract

Dystonia is an incurable movement disorder which can cause not only physical but also mental problems, leading to impaired health-related quality of life (HRQoL). For patients with dystonia refractory to medical treatment, deep brain stimulation (DBS) is a well-established surgical treatment. The objective of this systematic review is to provide a better understanding of HRQoL outcomes after DBS for dystonia. A search of the literature was conducted using Medline (PubMed), Embase, and Cochrane Library databases in May 2019. HRQoL outcomes after DBS along with motor outcomes were reported in a total of 36 articles involving 610 patients: 21 articles on inherited or idiopathic isolated dystonia, 5 on tardive dystonia, 3 on cerebral palsy, 2 on myoclonus-dystonia, 1 on X-linked dystonia-parkinsonism, and 3 on mixed cohorts of different dystonia subtypes. DBS improved motor symptoms in various subtypes of dystonia. Most studies on patients with inherited or idiopathic isolated dystonia showed significant improvement in physical QoL, whereas gains in mental QoL were less robust and likely related to the complexity of associated neuropsychiatric problems. HRQoL outcomes beyond 5 years remain scarce. Although the studies on patients with other subtypes of dystonia also demonstrated improvement in HRQoL after DBS, the interpretation is difficult because of a limited number of articles with small cohorts. Most articles employed generic measures (e.g. Short Form Health Survey-36) and this highlights the critical need to develop and to utilize sensitive and disease-specific HRQoL measures. Finally, long-term HRQoL outcomes and predictors of HRQoL should also be clarified.

1. Introduction

Dystonia is a movement disorder characterized by sustained or intermittent muscle co-contractions causing abnormal, often repetitive, movements, postures, or both [1]. This potentially debilitating disease can cause various problems, such as pain, depression, anxiety, social stigma, and reduced self-esteem, leading to impaired health-related quality of life (HRQoL) [2]. HRQoL encompasses the effects of a chronic disease and medical interventions on the patient’s physical, mental, and social aspects of living [3]. In the context of a chronic condition with only symptomatic treatments available, the main objective of care should be to improve or to maintain the patient’s HRQoL.

Deep brain stimulation (DBS) is a well-established surgical treatment for patients with dystonia refractory to medical treatment including botulinum toxin injections [4,5]. Recent meta-analyses and systematic reviews have shown that DBS effectively improves motor symptoms in patients with dystonia, especially in patients with inherited or idiopathic isolated dystonia (formerly, primary dystonia) [6–8]. The globus pallidus internus (GPi) remains the most common target and has been overall utilized more than the subthalamic nucleus (STN) or the thalamus. According to a recent systematic review summarizing the effects of DBS on non-motor symptoms in dystonia patients, GPi DBS reduced dystonia-related pain without significantly impacting anxiety, mood, and cognition [9]. Furthermore, the authors noted a potential dissociation or association between motor and non-motor response to DBS, which indicates motor assessments alone may not capture the true benefit of DBS.

Recent DBS studies reported HRQoL outcomes citing their increasing importance when investigating the overall efficacy of interventions [10–13]. Therefore, there is a need for an update on a systematic review of HRQoL outcomes after DBS [14,15]. In the present systematic review, we investigated the current literature related to HRQoL outcomes along with motor outcomes in patients with dystonia in order to gain a better understanding of the effects of DBS on HRQoL in dystonia when classified into different etiologies.

2. Methods

2.1. Search strategy

We conducted a systematic literature search from January 2000 to May 2019 using Medline (PubMed), Embase, and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The search terms included dystonia, torticollis, blepharospasm, Meige syndrome, hemidystonia, deep brain stimulation, DBS, pallidal stimulation, quality of life, QoL, HRQoL. The search syntax is provided in the Supplementary material. All records were independently screened for duplicates by two investigators (TT and JKW). Then, they independently performed title/ abstract screening and full-text assessments based on the eligibility criteria as described below. Disagreements were resolved through a discussion.

2.2. Eligibility criteria

The inclusion criteria for this systematic review were: (1) having a cohort of pediatric and/or adult patients with the diagnosis of inherited, idiopathic, or acquired dystonia (formerly, primary or secondary dystonia) [1], (2) DBS targeted to the GPi, STN, or thalamus, (3) reporting both motor and HRQoL outcomes using formal assessment scales, and (4) written in English. Conference papers, review articles, and meta-analyses were excluded. The reference lists of included publications were used for exploring additional publications.

3. Results

3.1. Literature search

The systematic literature search revealed a total of 548 records (Fig. 1). One additional article was found by exploring the reference lists of included articles. After removing 175 duplicated articles, we performed title and abstract screening for 374 articles to exclude nonhuman studies, non-DBS studies, and non-English articles and then examined the full texts of 201 remaining articles. Of these articles, 165 articles were excluded for the following reasons: review articles, meta-analyses, or conference papers (n = 88) or papers lacking motor/ HRQoL outcomes before and/or after DBS surgery (n = 77). Consequently, we identified 36 articles which reported both motor and HRQoL outcomes after DBS in dystonia patients.

Fig. 1.

Flow diagram of review process.

We sorted the 36 articles based on etiologies and associated features: 22 articles on inherited or idiopathic isolated dystonia (formerly, primary dystonia), 3 on combined inherited dystonia (X-linked dystonia-parkinsonism [XDP] and myoclonus-dystonia), 8 on acquired dystonia (tardive dystonia and cerebral palsy [CP]), and 3 on mixed cohorts of patients with different etiologies. When describing etiologies, we followed the original descriptions by the authors. Tables 1–3 present motor and HRQoL outcomes for patients with inherited or idiopathic isolated dystonia, inherited combined dystonia, and acquired dystonia, respectively.

Table 1.

Inherited or idiopathic isolated (primary) dystonia patients treated with deep brain stimulation.

Authors	Participants	Age at surgery (years)	Disease duration before surgery (years)	Target	Follow-up period	Motor improvementb	QOL items with significant improvement after DBSb
Vidailhet et al. (2005) [36]	22 generalized	30 (14–54)a	18 (4–37)a	Bil GPi	1 year	BFMDRS-M 51%	SF-36; physical functioning and role physical
Vidailhet et al. (2007) [4]	22 generalized	30 (14–54)a	18 (4–37)a	Bil GPi	3 years	BFMDRS-M 58%	SF-36; physical functioning, bodily pain, and general health
Mueller et al. (2008) [37]	40 (24 generalized, 16 segmental)	36.9 (N.A.)	17.9 (N.A.)	Bil GPi	6 months	BFMDRS-M 48%	SF-36; All 8 domains, PCS, and MCS
Volkmann et al. (2012) [31]	40 (24 generalized, 16 segmental)	36.9 (N.A.)	17.9 (N.A.)	Bil GPi	5 years	BFMDRS-M 58%	SF-36; physical functioning, role physical, bodily pain, general health, and vitality
Valldeoriola et al. (2010) [38]	24 (22 generalized, 2 segmental)	30 (N.A.)	10 (5–26)a	Bil GPi	1 year	BFMDRS-M 50%; BFMDRS-D 38%	SF-36; physical functioning, role physical, bodily pain, general health, role emotional, and PCS EQ-5D: mobility, self-care, usual activities, anxiety/depression and pain/discomfort
Tsuboi et al. (2019) [10]	16 (10 generalized, 6 segmental)	34.6 (8–67)	10.9 (2–32)	Bil GPi	10.9 (9–13) years	UDRS 41.6%	SF-36; role physical, MCS, and Total
Jahanshahi et al. (2014) [80]	14 generalized	41.9 (18–64)	24.1 (4–50)	Bil GPi	1.2 (0.4) years	BFMDRS-M 69%	No significant changes in EQ5D
Blahak et al. (2008) [72]	10 segmental	57.4 (35–77)	8.2 (1–20)	Bil GPi	1.4 (1.0–1.7) years	BFMDRS-M 62%	SF-36; physical functioning, role physical, general health, vitality, social functioning, mental health, PCS, MCS, and Total
Sakas et al. (2017) [13]	10 (8 generalized, 1 segmental, 1 focal)	35.8 (27–49)	17.3 (7–27)	Bil GPi	1 year	BFMDRS-M 54%; UDRS 55%; GDS 48.9%	SF-36: PCS and MCS tended to improve (not analyzed statistically)
Volkmann et al. (2014) [39]	62 cervical	56.9 (N.A.)	14.9 (N.A.)	Bil GPi	6 months	TWSTRS severity 28%; Tsui score 57%; Bain tremor score 66%	CDQ-24: 28% reduction at 6 months. SF-36: no significant differences between the active-stimulation and the sham-stimulation groups at 3 months.
Kiss et al. (2007) [75]	10 cervical	57.5 (47–64)	16.5 (5–28)	Bil GPi	1 year	TWSTRS: severity 43%, disability 64%, and pain 65%	SF-36: total
Bereznai et al. (2002) [73]	6 (1 generalized, 3 segmental, 2 focal)	52.3 (22–78)	15.8 (4–38)	Bil GPi	1 year	BFMDRS-M 73%; BFMDRS-D 76%; Tsui scale: 63% at 3 months	SF-36; physical functioning, bodily pain, vitality, social functioning, and mental health at 3–12 months
Shaikh et al. (2014) [81]	4 adult-onset axial	61.3 (53–67)	5.8 (2–15)	Bil GPi	2 years	BFMDRS-M 88%; TWSTRS severity 72%	SF-36: PCS and MCS tended to improve (not analyzed statistically)
Ostrem et al. (2017) [40]	20 (1 generalized, 16 segmental, 3 focal)	49.0 (17–70)	12.2 (2–33)	Bil STN	3 years	BFMDRS-M 70%; TWSTRS 67%	SF-36v2: total, physical and mental total, role physical, and bodily pain
Ostrem et al. (2011) [47]	9 predominantly cervical	47 (24–71)	10.9 (2–34)	Bil STN	1 year	TWSTRS total 62.9%	SF-36v2; physical component, physical functioning, role physical, and bodily pain
Cao et al. (2013) [41]	27 (distribution not described)	30.6 (7–76)	5.2 (2–12)	Bil STN	5.7 (3–10) years	BFMDRS-M 79%	SF-36; all 8 domains at 1 year and remained stable
Deng et al. (2018) [42]	14 (11 generalized, 1 segmental, 2 focal)	29.5 (10–76)	4.6 (1–12)	Bil STN	12.7 (11–15) years	BFMDRS-M 91%	SF-36; all 8 domains
Zhan et al. (2018) [43]	14 Meige syndrome	53.0 (39–65)	4.1 (1–11)	Bil STN	2.4 (1.0–4.3) years	BFMDRS-M 74%; BFMDRS-D 61% at 3 months	SF-36; all 8 domains
Kleiner-Fisman et al. (2007) [44]	4 (1 generalized, 3 segmental)	50.2 (41–56)	24.5 (10–39)	Bil STN	1 year	BFMDRS-M 25%; BFMDRS-D - 25%; TWSTRS severity 21%, disability 36%, and pain 24%	SF-36: improvement of PCS in 1 patient and of MCS in 3 (not analyzed statistically)
Lin et al. (2019) [45]	24 (16 generalized, 11 segmental, 1 multifocal, 2 focal)	37 (5–70)	5.1 (0.6–23)	Bil GPi for 14 Bil STN for 16	1 year	BFMDRS-M 48% for GPi and 64% for STN at 1 month	SF-36; all 8 domains both for GPi and STN
Schjerling et al. (2013) [46]	14 (4 generalized, 1 multifocal, 7 focal)	51 (32–68)	16.2 (3–30)	Bil GPi and STN for all patients	6 months	BFMDRS-M 8% for GPi and 44% for STN; TWSTRS 5% for GPi and 51% for STN	SF-36; PCS at 6 months. Statistics for 8 domains were not shown.
Starr et al. (2014) [82]	6 generalized	11.0 (7–15)	3.0 (1–6)	Bil GPi for 5 Bil STN for 1	1 year	BFMDRS-M 88%; BFMDRS-D 77%	SF-36v2: Total

Age at surgery, disease duration, and follow-up period are presented as mean (range) unless otherwise indicated.

^aMedian (range).

^bThe outcomes at the last follow-up are shown for motor improvement and QOL items with significant improvement after DBS unless otherwise indicated. N.A. = Not Assessed; Target: Bil = Bilateral, GPi = globus pallidus, STN = Subthalamic nucleus; Scales: BFMDRS-M = Burke-Fahn-Marsden Dystonia Rating Scale movement score, BFMDRS-D = Burke-Fahn-Marsden Dystonia Rating Scale disability score, CDQ-24 = Craniocervical Dystonia Questionnaire-24, EQ-5D = EuroQoL, SF-36 = Short Form Health Survey-36, SF-36v2 = Short Form Health Survey-36 version 2, TWSTRS = Toronto Western Spasmodic Torticollis Rating Scale, UDRS = Unified Dystonia Rating Scale.

Table 3.

Acquired dystonia patients treated with deep brain stimulation.

Authors	Participants	Age at surgery (years)	Disease duration before surgery (years)	Target	Follow-up period	Motor improvementa	QOL items with significant improvement after DBSa
Tardive dystonia
Gruber et al. (2018) [11]	25	58.4 (N.A.)	7.3 (N.A.)	Bil GPi	6 months	BFMDRS-M 42%; BFMDRS-D 19%; AIMS 38%	SF-36; physical and mental sum scores
Pouclet-Courtemanche et al. (2016) [60]	19	52.1 (25–69)	6.3 (1.4–38)	Bil GPi	Last follow-up in 14 patients ranged 6–11 years	ESRS 60%; AIMS 63%	Lehman Quality of Life Interview: general life satisfaction tended to improve at 6 months (n = 7)
Deng et al. (2017) [61]	10	29.8 (17–68)	N.A	Bil STN	5.5 (1.0–8.8) years	BFMDRS-M 88%; AIMS 94%	SF-36; all 8 domains
Gruber et al. (2009) [62]	9	63.2 (38–76)	5.3 (2–11)	Bil GPi	3.4 (1.5–6.7) years	BFMDRS-M 83%; BFMDRS-D 68%; AIMS 79%	SF-36; PCS, role physical, and social functioning
Woo et al. (2014) [63]	3	41.0 (28–49)	N.A	Bil GPi	3 months	BFMDRS-M 77%; GDS 66%	Improvement in EQ-5D (not analyzed statistically)
Cerebral palsy
Romito et al. (2015) [67]	15	29.8 (15–47)	25.4 (15–42) (age of dystonia onset)	Bil GPi	4.4 (2–7) years	BFMDRS-M 50%; BFMDRS-D 30%	SF-36; Total and all 8 domains
Vidailhet et al. (2009) [66]	13	32.6 (20–44)	N.A	Bil GPi	1 year	BFMDRS-M 24%	SF-36; bodily pain and mental health
Kim et al. (2019) [68]	12	29.3 (SD, 5.7)	N.A	Bil GPi	1 year	BFMDRS-M 37%; BFMDRS-D 2%	No significant improvement in SF-36
Mixed cohort
Hälbig et al. (2005) [69]	13 primary, 2 tardive	45.5 (13–68)	12.6 (2.5–40)	Bil GPi	6.5 (3–12) months	BFMDRS-M 60%; TWSTRS: severity 65%	Improvement in PDQ-39 by 37%
Kim et al. (2011) [70]	Group 1 (10 with cerebral palsy)	28.4 (18–37)	28.7 (17–39)	Group 1 A: Bil GPi; group 1 B, Bil GPi with thalamotomy	2.8 (1.0–7.4) years	Group 1 A BFMDRS-M 32%; BFMDRS-D 14%; Group 1 B: BFMDRS-M 32%; BFMDRS-D 10.2%	SF-36: physical functioning, bodily pain, vitality, social functioning, mental health
	group 2 (4 with trauma, 1 with tardive syndrome)	30.4 (23–40)	14.4 (3–23)	Bil or uni GPi	3.4 (2.0–5.8) years	BFMDRS-M 78%; BFMDRS-D 80%	SF-36: bodily pain, general health, vitality, social functioning, role emotional, mental health
Gimeno et al. (2012) [71]	5 with cerebral palsy, 1 with Glutaric Aciduria type I	9.8 (5–13)	9.8 (5–13)	Bil GPi	1 year	BFMDRS-M 6%; BFMDRS-D -1%	CPCHILD improved in 3 patients (not analyzed statistically)

Age at surgery, disease duration, and follow-up period are presented as mean (range) unless otherwise indicated.

^*Median (range).

^aThe outcomes at the last follow-up are shown for motor improvement and QOL items with significant improvement after DBS unless otherwise indicated. N.A. = Not Assessed; Target: Bil = Bilateral, GPi = globus pallidus, STN = Subthalamic nucleus; Scales: AIMS = Abnormal Involuntary Movement Scale, BFMDRS-M = Burke-Fahn-Marsden Dystonia Rating Scale movement score, BFMDRS-D = Burke-Fahn-Marsden Dystonia Rating Scale disability score, CPCHILD = Child Health Index of Life with Disabilities questionnaire, EQ-5D = EuroQoL, ESRS = Extrapyramidal Symptoms Rating Scale, GDS = Global Dystonia Rating Scale, PDQ-39 = Parkinson’s Disease Questionnaire-39, SF-36 = Short Form Health Survey-36, TWSTRS = Toronto Western Spasmodic Torticollis Rating Scale.

3.2. Scales for motor and HRQoL assessments

To assess dystonia symptoms, most articles (n = 31) employed the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) which comprised the motor part (BFMDRS-M) and the disability part of the scale (BFMDRS-D) [16]. Some articles used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) [17], the Tsui scale [18], the Unified Dystonia Rating Scale (UDRS) [19], and the Global Dystonia Rating Scale (GDS) [19]. The Extrapyramidal Symptoms Rating Scale (ESRS) [20] and the Abnormal Involuntary Movement Scale (AIMS) [21] were used to assess movement disorders in patients with tardive dystonia. In Addition, the Unified Myoclonus Rating Scale (UMRS) [22] and the Unified Parkinson’s Disease Rating Scale (UPDRS) [23] were used to assess myoclonus in myoclonus-dystonia patients and parkinsonism in XDP patients, respectively.

For HRQoL assessments, Short Form Health Survey-36 (SF-36) [24] or its newer version (SF-36v2; Optum, Inc. https://www.optum.com/solutions.html. Accessed 2019 August 4) were the most commonly used instruments (30 articles). The EuroQoL (EQ-5D) was used in three articles [25], the Child Health Index of Life with Disabilities questionnaire (CPCHILD) in 2 [26], the Craniocervical Dystonia Questionnaire-24 (CDQ-24) in 1 [27], the Parkinson’s Disease Questionnaire-39 (PDQ-39) in 1 [28], and the Lehman Quality of Life Interview in 1 [29].

The SF-36 is one of the most widely used generic instruments of HRQoL and measures eight health dimensions: physical functioning, role physical (role limitations due to physical health issues), bodily pain, general health, vitality, social functioning, role emotional (role limitations due to personal or emotional issues), and mental health. The newer version of the SF-36 (SF-36v2) has comparable domains with previous SF-36 scores. Table 4 present HRQoL outcomes according to SF-36. The data for the eight health domains were available only in the figures without the values in 4 articles and were not available in 7. The physical component summary (PCS) and mental component summary (MCS) scores were shown in 12 articles, and the SF-36 Total score was shown in 5. Although there are a few different reported methods for calculating SF-36 Total scores, most authors did not specify the methods of calculation. This issue has been discussed elsewhere [30]. Furthermore, 6 articles provided only PCS/MCS or Total scores without presenting the data for the eight health domains of SF-36. This variability in the outcome data presentation of the eight domains, PCS/MCS, and Total scores rendered interpretation somewhat difficult.

Table 4.

SF-36 data at baseline and the last follow-up.

Authors			Physical functioning	Role physical	Bodily pain	General health	Vitality	Social functioning	Role emotional	Mental health	PCS	MCS	Total
Inherited or idiopathic isolated dystonia
Vidailhet et al. (2005) [36]	GPi	Baseline	41 ± 28	53 ± 43	39 ± 32	47 ± 24	40 ± 24	57 ± 36	59 ± 48	54 ± 20	NA	NA	NA
		1 year	62 ± 29 a	58 ± 39	56 ± 36	63 ± 27 a	50 ± 24	58 ± 29	77 ± 37	64 ± 23	NA	NA	NA
Vidailhet et al. (2007) [4]	GPi	Baseline	41 ± 28	53 ± 43	39 ± 32	47 ± 24	40 ± 24	57 ± 36	59 ± 48	54 ± 20	NA	NA	NA
		3 year	68 ± 32 a	69 ± 37	61 ± 25 a	64 ± 21 a	47 ± 21	63 ± 30	71 ± 39	58 ± 21	NA	NA	NA
Kupseh et al. (2006) [5]	GPi	Baseline	39.1 ± 22.5	31.1 ± 37.5	44.8 ± 29.6	42.2 ± 15.7	45.7 ± 20.9	59.2 ± 36.0	62.3 ± 42.6	60.0 ± 19.8	33.7 ± 7.7	46.2 ± 13.2	NA
		6 months	62.0 ± 28.7 a	64.5 ± 38.4 a	76.0 ± 29.3 a	60.7 ± 22.5 a	57.8 ± 21.8 a	76.0 ± 29.3 a	79.8 ± 35.l a	72.2 ± 21.l a	44.1 ± 9.1 a	51.8 ± 11.8 a	NA
Volkmann et al. (2012) [31]	GPi	Baseline	39.1 ± 22.5	31.1 ± 37.5	44.8 ± 29.6	42.2 ± 15.7	45.7 ± 20.9	59.2 ± 36.0	62.3 ± 42.6	60.0 ± 19.8	NA	NA	NA
		5 years	65.0 ± 26.8 a	71.8 ± 35.8 a	73.9 ± 28.1 a	63.1 ± 16.8 a	58.4 ± 16.3 a	77.9 ± 27.6	83.9 ± 35.2	69.5 ± 20.2	NA	NA	NA
Valldeoriola et al. (2010) [38]	GPi	Baseline	IF	IF	IF	IF	IF	IF	IF	IF	IF	IF	NA
		1 year	IF a	IF a	IF a	IF a	IF	IF	IF a	IF	IF a	IF	NA
Tsuboi et al. (2019) [10]	GPi	Baseline	60.3 ± 30.1	37.5 ± 44.7	52.9 ± 28.9	63.7 ± 12.7	54.7 ± 20.0	66.6 ± 28.7	70.8 ± 38.3	73.0 ± 20.1	39.5 ± 9.6	46.1 ± 10.1	42.8 ± 9.4
		≥9 yrs	61.6 ± 34.9	71.9 ± 32.8 a	61.7 ± 23.7	69.5 ± 18.5	60.3 ± 24.5	77.4 ± 21.9	85.4 ± 34.3	81.8 ± 15.5	43.9 ± 10.2	51.5 ± 9.1 a	47.7 ± 8.3 a
Blahak et al. (2008) [72]	GPi	Baseline	IF	IF	IF	IF	IF	IF	IF	IF	IF	IF	IF
		17 months	IF a	IF a	IF	IF a	IF a	IF a	IF	IF a	IF a	IF a	IF a
Sakas et al. (2017) [13]	GPi	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	38.4	56.2	NA
		6 months	NA	NA	NA	NA	NA	NA	NA	NA	34.7	50.1	NA
Volkmann et al. (2014) [39]	GPi	Baseline	63.5 ± 26.0	42.5 ± 44.1	41.5 ± 27.5	45.6 ± 18.1	46.1 ± 17.3	53.6 ± 25.3	52.2 ± 45.2	51.9 ± 18.2	NA	NA	NA
		3 months	70.5 ± 24.7	51.7 ± 42.0	62.5 ± 26.4	58.6 ± 17.4	55.5 ± 16.6	66.3 ( 27.3	48.9 ± 48.5	62.5 ± 17.3	NA	NA	NA
Kiss et al. (2007) [75]	GPi	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	90.9 ± 11.3
		1 year	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	112.9 ± 18.0 a
Bereznai et al. (2002) [73]	GPi	Baseline	IF	IF	IF	IF	IF	IF	IF	IF	NA	NA	NA
		1 year	IF a	IF	IF a	IF	IF a	IF a	IF	IF a	NA	NA	NA
Shaikh et al. (2014) [81]	GPi	Baseline	IF	IF	IF	IF	IF	IF	IF	IF	27.6 ± 12.9	51.5 ± 10.3	NA
		1 year	IF	IF	IF	IF	IF	IF	IF	IF	IF	IF	NA
Ostrem et al. (2017) [40]	STN	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	45.1 ± 20.0
		36 months	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	65.8 ± 23.0
Ostrem et al. (2011) [47]	STN	Baseline	27.8	28.6	30.1	44.2	32.6	27.2	26.4	32.5	32.9	31.7	NA
		12 months	41.3 a	36.7 a	41.2 a	40.6	37.5	28.4	30.1	33.7	43.7 a	29.3	NA
Cao et al. (2013) [41]	STN	Baseline	26 ± 28	14 ± 20	48 ± 14	15 ± 7	33 ± 11	31 ± 7	12 ± 19	35 ± 13	NA	NA	NA
		3–10 years	76 ± 18	72 ± 24	73 ± 10	65 ± 10	68 ± 12	70 ± 17	71 ± 26	67 ± 9	NA	NA	NA
Deng et al. (2018) [42]	STN	Baseline	21 ± 22	13 ± 16	49 ± 10	16 ± 7	34 ± 9	21 ± 8	12 ± 17	33 ± 11	NA	NA	NA
		10 years	85 ± 18 a	82 ± 28 a	81 ± 9 a	68 ± 9 a	81 ± 9 a	68 ± ll a	95 ± 12 a	80 ± 7 a	NA	NA	NA
Zhan et al. (2018) [43]	STN	Baseline	26 ± 23	32 ± 23	56 ± 23	21 ± 7	19 ± 12	32 ± 11	40 ± 23	29 ± 13	NA	NA	NA
		28.5 months	71 ± 18 a	64 ± 21 a	83 ± 18 a	60 ± 14 a	62 ± 16 a	75 ± 12 a	76 ± 28 a	65 ± 16 a	NA	NA	NA
Kleiner-Fisman et al. (2007) [44]	STN	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	IF	IF	NA
		1 year	NA	NA	NA	NA	NA	NA	NA	NA	IF	IF	NA
Lin et al. (2019) [45]	GPi	Baseline	22 ± 22	19 ± 39	49 ± 14	19 ± 5	34 ± 8	33 ± 19	17 ± 17	35 ± 16	NA	NA	NA
		1 year	88 ± 22	86 ± 33	71 ± 7	68 ± 7	76 ± 13	81 ± 21	85 ± 34	69 ± 14	NA	NA	NA
Lin et al. (2019) [45]	STN	Baseline	46 ± 27	23 ± 33	50 ± 14	19 ± 6	40 ± 6	38 ± 13	22 ± 22	36 ± 17	NA	NA	NA
		1 year	84 ± 19	73 ± 25	72 ± 8	65 ± 9	72 ± 5	73 ± 18	63 ± 33	69 ± 14	NA	NA	NA
Schjerling et al. (2013) [46]	GPi/STN	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	Not specified	Not specified	NA
		6 months	NA	NA	NA	NA	NA	NA	NA	NA	Not specified	Not specified	NA
Starr et al. (2014) [82]	GPi/STN	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	53.5 ± 13.7
		1 year	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	81.7 ± 13.3 a
X-linked Dystonia Parkinsonism (DYT3)
Brüggemann et al. (2019) [52]	GPi	Baseline	40.7 ± 24.7	17.9 ± 33.1	37.0 ± 19.0	31.8 ± 18.7	42.1 ± 17.3	42.0 ± 22.8	45.2 ± 46.4	60.9 ± 22.9	NA	NA	NA
		15.7 months	51.4 ± 24.4	44.6 ± 39.4	72.5 ± 22.7 a	62.9 ± 26.7 a	56.0 ± 21.8	67.9 ± 22.3 a	61.9 ± 41.0	82.0 ± 19.1 a	NA	NA	NA
Myoclonus dystonia
Gruber et al. (2010) [56]	GPi/Vim	Baseline	52.1 ± 33.8	21.4 ± 22.5	58.4 ± 35.9	42.0 ± 17.3	45.0 ± 22.0	50.0 ± 33.1	47.6 ± 50.4	53.1 ± 23.3	36.3 ± 8.5	40.2 ± 15.0	NA
		Not specified	45.7 ± 26.4	46.4 ± 46.6	69.1 ± 35.0	50.8 ± 17.9 a	46.4 ± 26.1	78.6 ± 35.9	42.9 ± 53.5	57.7 ± 28.1	39.9 ± 9.4	43.7 ± 16.0	NA
Rocha et al. (2016) [57]	GPi	Baseline	92.5	39	75	50	46.9	50	83.3	65	NA	NA	NA
		1 year	97.5	100	90	82.5	59.4	93.8	100	72.5	NA	NA	NA
Tardive dystonia
Gruber et al. (2018) [11]	GPi	Baseline	NA	NA	NA	NA	NA	NA	NA	NA	30.4 ± 7.4	40.0 ± 12.5	NA
		6 months	NA	NA	NA	NA	NA	NA	NA	NA	35.8 ± 9.9 a	46.1 ± 10.9 a	NA
Deng et al. (2017) [61]	STN	Baseline	29.5 ± 35.3	10.0 ± 21.1	36.1 ± 30.7	37.5 ± 14.8	30.5 ± 22.5	23.8 ± 13.8	26.6 ± 21.1	28.4 ± 14.5	NA	NA	NA
		5.5 years	90.5 ± 30.0 a	87.5 ± 31.7 a	81.6 ± 19.2 a	81.6 ± 19.2 a	69.0 ± 17.3 a	69.0 ± 17.3 a	93.2 ± 21.l a	73.2 ± 12.5 a	NA	NA	NA
Gruber et al. (2009) [62]	GPi	Baseline	32.9 ± 29.0	14.3 ± 28.3	48.1 ± 37.5	38.6 ± 12.1	34.3 ± 20.3	44.6 ± 27.8	57.1 ± 53.5	42.9 ± 30.6	30.6 ± 9.6	38.9 ± 12.8	NA
		3.4 yars	49.3 ± 31.1	75.0 ± 38.2 a	76.3 ± 18.0	46.6 ± 19.3	57.1 ± 24.5	66.1 ± 31.2 a	66.6 ± 47.1	61.7 ± 14.2	42.6 ± 12.6 a	45.9 ± 9.4	NA
Cerebral pulsy
Romito et al. (2015) [67]	GPi	Baseline	15.7 ± 13.2	3.3 ± 8.8	26.2 ± 12.3	69.3 ± 5.1	39.3 ± 8.2	13.1 ± 12.0	59.6 ± 28.7	54.9 ± 9.6	NA	NA	281.5 ± 37.4
		4.4 yars	50.0 ± 33.0 a	56.7 ± 24.0 a	69.1 ± 17.l a	73.0 ± 8.6 a	58.0 ± 10.7 a	38.2 ± 17.3 a	90.6 ± 15.6 a	73.9 ± 6.9 a	NA	NA	509.7 ± 93.6 a
Vidailhet et al. (2009) [66]	GPi	Baseline	54.2 ± 29.9	56.9 ± 39.0	61.0 ± 31.6	67.3 ± 22.7	51.2 ± 27.3	64.4 ± 21.0	35.9 ± 37.2	52.6 ± 22.6	NA	NA	NA
		1 year	57.7 ± 34.4	61.5 ± 40.3	79.5 ± 25.9 a	61.5 ± 40.3	53.5 ± 20.1	65.4 ± 27.6	57.7 ± 34.4	65.5 ± 18.2 a	NA	NA	NA
Kim et al. (2019) [68]	GPi	Baseline	53.9 ± 21.0	71.9 ± 18.6	59.8 ± 24.3	66.7 ± 20.1	59.0 ± 21.6	60.8 ± 26.1	79.2 ± 20.3	59.4 ± 17.7	NA	NA	NA
		1 year	52.2 ± 20.6	71.9 ± 17.0	74.2 ± 20.8	66.0 ± 21.2	64.6 ± 25.7	64.2 ± 26.1	75.0 ± 18.1	61.9 ± 21.8	NA	NA	NA

Mean ± SD are presented if available. IF indicates that the data was shown only in the figures and that the values were not available.

^aIndicates a significant difference compared with the baseline. NA indicates that the data was not assessed. GPi = globus pallidus, MCS = mental component summary; PCS = physical component summary; STN = Subthalamic nucleus; SF-36 = Short Form Health Survey-36; Vim = ventral intermediate nucleus.

3.3. Inherited or idiopathic isolated dystonia

3.3.1. GPi DBS

Most studies on patients with generalized or segmental dystonia reported motor improvement according to the BFMDRS-M after bilateral GPi DBS with a range between 40% and 80% at short-term (e.g., 1 year) [6]. Prospective clinical trials have shown sustained motor and HRQoL improvement for up to 5 years, which will be discussed in the following paragraphs [4,31]. In addition, a few retrospective studies reported favorable motor outcomes beyond 5 years in most cases without showing HRQoL data [10,32–35].

In a French prospective, controlled, multicenter study on 22 patients with primary generalized dystonia, BFMDRS-M improved by 51% at 1 year and 58% at 3 years after bilateral GPi DBS [4,36]. Significant HRQoL improvement according to SF-36 was observed in general health and physical functioning at 1 year and general health, physical functioning, and pain at 3 years. Cognition and mood were unmodified during the follow-up.

In an international, randomized, controlled trial (RCT), 40 primary segmental or generalized dystonia patients were randomly assigned to either the active-stimulation group or the sham-stimulation group for 3 months [5,37]. At 3 months, the improvement from baseline in BFMDRS-M was significantly greater in the active-stimulation group than in the sham-stimulation group (39.3% vs. 4.9%, respectively); and the active-stimulation group experienced significantly better improvement in HRQoL (physical functioning, bodily pain, general health, vitality, social functioning, and PCS). In the open-label extension phase with both groups being actively treated, sustained improvement in BFMDRS-M was observed (47.9% at 6 months, 61.1% at 3 years, and 57.8% at 5 years) [31]. All the eight domains of SF-36 significantly improved at 6 months [37]. All the domains remained relatively stable from 6 months to 5 years, but only five domains reached statistical significance when compared with the baseline status (general health, physical functioning, role physical, bodily pain, and vitality) [31].

In a Spanish prospective, multicenter study [38], 24 primary generalized or segmental dystonia patients had 50% improvement in BFMDRS-M after GPi DBS at 1 year compared with the baseline status; HRQoL domains according to SF-36 (physical functioning, role physical, bodily pain, general health, role emotional, and PCS) and EQ-5D (mobility, self-care, usual activities, anxiety/depression, and pain/discomfort) also significantly improved.

A retrospective study on 16 isolated generalized or segmental dystonia patients treated with GPi DBS showed that a significant improvement was maintained up to ≥9 years only in the role physical domain of SF-36 compared with baseline [10]. Significant improvements in SF-36 Total, PCS, and MCS were found at 1–2 years whereas improvements remained significant at ≥ 9 years only for Total and MCS.

In an RCT, 62 patients with cervical dystonia were randomly assigned to either the active-stimulation group or the sham-stimulation group for 3 months [39]. The primary outcome, improvement in TWSTRS severity score, was significantly greater in the active-stimulation group (26%) than in the sham-stimulation group (6%), but there were no significant differences in improvement of quality of life (CDQ-24 and SF-36) between the two groups, possibly because of the short follow-up period. At 6 months with both groups being actively treated, a significant reduction in CDQ-24 by 28% was observed, but the data from the SF-36 were not shown.

3.3.2. STN DBS

Most studies reported motor improvement according to the BFMDRS-M after bilateral STN DBS with a range between 40% and 80% similar to the outcomes of GPi DBS [40–46]. In a prospective study on 20 isolated dystonia patients with prominent cervical involvement, dystonia symptoms improved at 3 years by 70% and 67% according to BFMDRS-M and TWSTRS, respectively [40]. SF-36v2 showed significant improvement in bodily pain, role physical, PCS, MCS, and Total scores at 3 years. This group also reported comparable motor and HRQoL outcomes 1 year after STN DBS in a smaller cohort of patients with primary predominantly cervical dystonia (n = 9) [47]. A Chinese group also reported exceptionally favorable long-term motor and HRQoL outcomes of STN DBS for patients with primary dystonia; All the eight domains of SF-36 showed sustained improvement at the last follow-ups (2.4–12.7 years after surgery) [41–43].

3.3.3. GPi vs STN

A few studies compared the effects of GPi and STN DBS in patients with primary dystonia. In one study, motor improvement at 6 months was smaller with GPi DBS than with STN DBS; however, this result may be at least partially attributable to the suboptimal GPi lead positions in a subset of patients [46]. HRQoL outcomes were not compared between GPi and STN DBS. In another study, GPi and STN DBS showed comparable motor improvement with similar HRQoL improvements at 1 month; all of the eight domains in SF-36 significantly improved in both groups [45].

3.4. Inherited combined dystonia

XDP, also called DYT3, is featured by adult-onset dystonia, which rapidly generalizes within a few years [48]. In most patients, parkinsonism becomes more pronounced than dystonia in the later disease course. Case reports and small case series reported beneficial effects of GPi DBS both on dystonia and parkinsonism [49–51]. A recent prospective cohort study analyzed GPi DBS outcomes for 16 Filipino men with DYT3 [52]. Masked video ratings revealed significant improvements of BFMDRS-M by 59% at 6 months after surgery. Parkinsonism, according to UDPRS-III, also improved at 6 months (27%). The improvement in parkinsonism was smaller than that in dystonia. Unmasked long-term observation up to 46 months showed the sustained efficacy of GPi-DBS both on dystonia and parkinsonism. As for HRQoL according to SF-36, bodily pain, general health, social functioning, and mental health significantly improved at a mean follow-up of 15.7 months after surgery.

Myoclonus-dystonia is characterized by lightning-like myoclonic jerks and dystonic symptoms which usually emerges in the first two decades of life [53]. In most patients with myoclonus-dystonia, mutations in the epsilon-sarcoglycan gene (SGCE) gene are found (DYT11). A pooled analysis of 40 patients with myoclonus-dystonia who underwent GPi and/or ventral intermediate nucleus (Vim) DBS showed improvement in myoclonus by 72.6% and in dystonia by 52.6% at a mean follow-up of 27.2 months [54]. Intriguingly, GPi and Vim DBS had comparable beneficial effects on myoclonus, whereas improvement in dystonia was greater with GPi than Vim DBS. A recent prospective study showed the long-term efficacy of GPi DBS both on myoclonus and dystonia at a mean follow-up of 8.7 years [55].

There have been two small studies which assessed both motor and HRQoL outcomes of DBS for myoclonus-dystonia. In a study of 10 patients with myoclonus-dystonia (9 SGCE-mutation positive and 1 negative), 8 patients received bilateral GPi and Vim DBS, 1 received bilateral Vim DBS, and 1 received bilateral GPi DBS [56]. The patients experienced improvement in myoclonus (65.5% according to UMRS) and dystonia (48.2% according to BFMDRS-M) at a mean follow-up of 62.3 months. Significant HRQoL improvement according to SF-36 was observed in general health. Another study on 2 patients with myoclonus-dystonia (1 SGCE-mutation positive and 1 negative) reported improvement in BFMDRS-M and UMRS at 1 year (62% and 80%, respectively) [57]. Some domains of the SF-36v2 (role physical, general health, and social functioning) showed prominent improvement at 1 year after surgery, but no statistical analysis was done.

3.5. Tardive dystonia

Tardive dystonia refers to a dystonia/dyskinesia syndrome associated with exposure to dopamine receptor blocking agents [58]. In contrast to other types of acquired dystonia, tardive dystonia is known to respond well to DBS [59]. An RCT of bilateral GPi DBS for 25 patients with tardive dystonia failed to see the significantly better motor outcomes in the active-stimulation group over the sham-stimulation group at 3 months [11]. However, the patients had significant improvement in BFMDRS-M by 41.5% and AIMS by 38% after 6 months of the open-label extension with all patients being actively treated. In addition, PCS and MCS of SF-36 improved significantly at 6 months, but the data for the eight domains were not provided.

Some other studies reported the long-term efficacy of GPi or STN DBS on tardive dystonia with variable assessment scales as summarized in Table 3 [60–63]. One study found that, after GPi DBS, HRQoL domains according to SF-36 (role physical, and social functioning, and PCS) significantly improved at a mean follow-up of 3.4 years [62]. Another study reported that general life satisfaction tended to improve 6 months after GPi DBS [60]. Finally, STN DBS improved all the eight domains of SF-36 at a mean follow-up of 5.5 years [61].

3.6. Cerebral palsy

CP is a group of permanent disorders of the development of movement and posture due to non-progressive disturbances that occurred in the developing fetal or infant brain [64]. Dyskinetic CP accounts for 10–15% of patients and presents with severe hyperkinetic movement disorders with little or no cognitive impairment, and DBS has been used primarily for patients with this phenotype. A meta-analysis showed a significant improvement of BFMDRS-M on average by 23.6% in patients with CP after DBS [65]. Responses to DBS in patients with CP vary likely related in large part to the heterogeneous etiologies of this syndrome.

In a multicenter prospective study, GPi DBS outcomes were analyzed in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI [66]. BFMDRS-M significantly improved by 24.4% one year after surgery. HRQoL domains of SF-36 (bodily pain and mental health) also significantly improved at 1 year.

Another study on 15 patients with dystonia due to CP reported improvement of BFMDRS-M by 49.5% at a mean follow-up of 4.4 years, which was concurrent with significant improvement in all the eight domains of SF-36 [67].

A retrospective study compared the efficacy of GPi DBS and intrathecal baclofen (ITB) therapy [68]. Only patients who underwent GPi DBS had significant improvement in BFMDRS-M after surgery; however, HRQoL did not improve significantly in patients treated with GPi DBS. Despite the non-significant improvement in motor function, patients treated with ITB therapy showed significant improvement in some domains of the SF-36.

3.7. Mixed cohorts

Three studies with mixed cohorts of dystonia subtypes (primary dystonia, tardive dystonia, CP, post-traumatic dystonia, and glutaric aciduria type I) reported motor and HRQoL outcomes of GPi DBS (Table 3) [69–71]. A cohort of 13 patients with primary dystonia and 2 with tardive dystonia experienced significant HRQoL improvement by 37% according to PDQ-39 along with motor and disability improvement after GPi DBS [69]. In another study, 10 CP patients had significant improvement in physical functioning, body pain, vitality, social functioning, and mental health after GPi DBS, whereas a group of 4 patients with post-traumatic dystonia and 1 with tardive dystonia had significant improvement in bodily pain, general health, vitality, social functioning, role emotional, and mental health [70]. In a study on a cohort of 5 patients with CP and 1 with Glutaric Aciduria type I, significant improvement in CPCHILD was found only in 3 patients with CP after GPi DBS [71].

4. Discussion

This systematic review analyzed HRQoL outcomes along with motor outcomes after DBS from a total of 36 articles involving 610 patients with various subtypes of dystonia. Patients with inherited or idiopathic isolated dystonia are likely to experience improvement in physical QoL. In contrast, benefits in mental QoL may be less robust, probably because of the complexity of neuropsychiatric conditions. Some studies also showed favorable HRQoL outcomes in patients with tardive dystonia, CP, myoclonus-dystonia, and XDP; however, the available data have been limited.

Most articles on inherited or idiopathic isolated dystonia patients reported significant improvement in physical QoL (physical functioning, role physical, bodily pain, and general health) [4,5,10,31, 36,40–43,45,47,72,73]. The physical functioning and role physical domains of SF-36 assess physical disability similar to BFMDRS-D, and TWSTRS disability scores. Many studies reported significant improvement in these scores along with motor improvement following surgery [4,5,31,36,38,42,43,47,72,73]. Pain is known to be one of the major determinants of HRQoL [2,74]. Bodily pain of SF-36 showed significant improvement in most studies [4,5,10,31,38,40–43,45,47,73], which was consistent with the outcomes assessed with the scales specific to pain problems [5,34,38,39,75,76]. The general health scale of the SF-36 also significantly improved, suggesting that the patients’ overall life satisfaction improved after DBS surgery [4,5,31,41–43,45,72].

In contrast to relatively robust improvement in physical QoL, only a small proportion of the articles including patients with inherited or idiopathic isolated dystonia reported significant improvement in mental QoL (vitality, social functioning, role emotional, and mental health) [5,10,31,38,41–43,45,72,73]. This may have been a result of mental QoL being affected by multiple factors, such as school life, employment status, marital status, and mood disorders [2]. Therefore, the improved motor function may not guarantee a gain in mental QoL. In addition, multiple issues related to HRQoL remain unexplored, such as the impact of DBS on employment or marital status in adults and school performance in children, which should be investigated in future studies.

In this regard, qualitative research on patients with isolated dystonia who underwent DBS may provide essential insights into how to enhance patients’ mental QoL [77]. After DBS, patients had to adapt from a life with limited physical and social activities to one with significantly more opportunities. Patients regularly seek professional guidance and support during this challenging transition time. Psychological disorders and social maladjustment may possibly be addressed through a comprehensive perioperative approach including a team with neurologists, neurosurgeons, psychiatrists, psychologists, nurses, rehabilitation therapists, and social workers.

As described in the Results section, prospective clinical trials have shown sustained HRQoL improvement after GPi DBS for up to 5 years [4,31]. A retrospective study suggested the gain in HRQoL after GPi DBS waned ≥9 years of follow-up possibly because of disease progression in a subset of patients [10]. Another group reported sustained HRQoL improvements after STN DBS for over 5 years [41,42]. However, more data on long-term HRQoL outcomes are needed.

To the best of our knowledge, only one study has analyzed predictors of HRQoL outcomes after DBS in dystonia patients [10]. This study on 16 patients with inherited or idiopathic isolated dystonia reported that HRQoL outcomes were not predicted by any of the baseline characteristics (age at onset, age at DBS, disease duration before surgery, body distribution, preoperative motor scores) and that SF-36 outcomes at short-term follow-up predicted those at the long-term. In patients with dystonia outside the context of DBS, the most critical determinants of worse HRQoL were reported to be depression and anxiety [2]. The impact of these neuropsychiatric symptoms on HRQoL outcomes after DBS should also be analyzed in future studies.

The development of sensitive and disease-specific measures to assess the HRQoL for dystonia patients is vital. Most articles employed generic HRQoL measures (e.g. SF-36 or EQ-5D) presumably because of a lack of disease-specific HRQoL measures in these populations. For patients with cervical dystonia, the combination of the TWSTRS-2 and Cervical Dystonia Impact Profile-58 were validated as a rating scale covering the aspects of motor, disability, pain, psychiatric problems, and HRQoL [78]. Similar comprehensive scales are needed for the other subtypes of dystonia.

There remain several shortcomings worth mentioning. First, we found a limited number of articles related to HRQoL in myoclonus-dystonia, XDP, tardive dystonia, CP, post-traumatic dystonia, and glutaric aciduria type I. Although some articles reported the beneficial effects of DBS either on physical or mental QoL in these populations, it is difficult to interpret these findings because of a limited number of articles with small cohorts [11,52,57,61,62,66,67]. Furthermore, HRQoL data for patients with different types of acquired dystonia are not available. Second, the impact of genetic mutation on HRQoL outcomes have never been evaluated. Earlier studies suggested distinct motor outcomes among patients with or without specific genetic mutations, such as DYT1 or DYT6 [6,79]. The relationship between the genetic status and HRQoL outcomes should be explored. Third, most studies presented HRQoL changes following DBS only in terms of statistical significance. Their clinical meaningfulness should be assessed in future studies.

5. Conclusion

This systematic review demonstrated favorable HRQoL outcomes, especially physical QoL, in patients with inherited or idiopathic isolated dystonia. Benefits in mental QoL may be less robust, and a multidisciplinary approach would be helpful. Future studies should clarify long-term HRQoL outcomes, predictors for HRQoL outcomes, and the contribution of genetic factors. More HRQoL data for patients with inherited combined dystonia or acquired dystonia are also needed. In addition, the development of sensitive and disease-specific measures is required for different subtypes of dystonia. Collectively, results from future studies would allow clinicians to provide patients with clearer perspective and to enhance patients’ HRQoL following DBS.

Table 2.

Inherited combined dystonia patients treated with deep brain stimulation.

Authors	Participants	Age at surgery (years)	Disease duration before surgery (years)	Target	Follow-up period	Motor improvementa	QOL items with significant improvement after DBSa
X-linked Dystonia Parkinsonism (DYT3)
Brüggemann et al. (2019) [52]	16	40.9 (30–52)	3.2 (1–6)	Bil GPi	46 months	BFMDRS-M 59%; UPDRS III (27%) at 6 months	SF-36; bodily pain, general health, social functioning, and mental health at a mean FU of 15.7 months
Myoclonus dystonia
Gruber et al. (2010) [56]	10 (9 SGCE positive and 1 negative)	43.5 (24–69)	37.4 (19–63)	Bil GPi + Vim for 8; Bil GPi for 1; Bil Vim for 1	62.3 (15–128) months	BFMDRS-M 48%; Tsui scale 35%; UMRS 66%	SF-36; general health
Rocha et al. (2016) [57]	2 (1 SGCE positive and 1 negative)	18.5 (17–20)	14.5 (11–18)	Bil GPi	1 year	BFMDRS-M 62%; BFMDRS-D 73%; UMRS 80%	SF-36v2; prominent improvement in role physical, general health, and social functioning (not analyzed statistically)

Age at surgery, disease duration, and follow-up period are presented as mean (range).

^aThe outcomes at the last follow-up are shown for motor improvement and QOL items with significant improvement after DBS unless otherwise indicated. Target: Bil = Bilateral, GPi = globus pallidus, Vim = ventral intermediate nucleus; Scales: BFMDRS-M = Burke-Fahn-Marsden Dystonia Rating Scale movement score, BFMDRS-D = Burke-Fahn-Marsden Dystonia Rating Scale disability score, SF-36 = Short Form Health Survey-36, SF-36v2 = Short Form Health Survey-36 version 2, UMRS = Unified Myoclonus Rating Scale, UPDRS = Unified Parkinson’s Disease Rating Scale.