Background: Deep brain stimulation (DBS) has been utilized for over two decades to treat medication-refractory dystonia in children. Short-term benefit has been demonstrated for inherited, isolated, and idiopathic cases, with less efficacy in heredodegenerative and acquired dystonia. The ongoing publication of long-term outcomes warrants a critical assessment of available information as pediatric patients are expected to live most of their lives with these implants. Summary: We performed a review of the literature for data describing motor and neuropsychiatric outcomes, in addition to complications, 5 or more years after DBS placement in patients undergoing DBS surgery for dystonia at an age younger than 21. We identified 20 articles including individual data on long-term motor outcomes after DBS for a total of 78 patients. In addition, we found five articles reporting long-term outcomes after DBS in 9 patients with status dystonicus. Most patients were implanted within the globus pallidus internus, with only a few cases targeting the subthalamic nucleus and ventrolateral posterior nucleus of the thalamus. The average follow-up was 8.5 years, with a range of up to 22 years. Long-term outcomes showed a sustained motor benefit, with median Burke-Fahn-Marsden dystonia rating score improvement ranging from 2.5% to 93.2% in different dystonia subtypes. Patients with inherited, isolated, and idiopathic dystonias had greater improvement than those with heredodegenerative and acquired dystonias. Sustained improvements in quality of life were also reported, without the development of significant cognitive or psychiatric comorbidities. Late adverse events tended to be hardware-related, with minimal stimulation-induced effects. Key Messages: While data regarding long-term outcomes is somewhat limited, particularly with regards to neuropsychiatric outcomes and adverse events, improvement in motor outcomes appears to be preserved more than 5 years after DBS placement.

Dystonia is a movement disorder defined by involuntary sustained or intermittent muscle contractions, typically described as patterned and twisting postures. They are commonly action-induced, may be associated with tremor or overflow muscle activation, and are alleviated by a “sensory trick.” Pediatric dystonia is defined by the onset at less than 21 years of age, with a prevalence estimated at 2–50 cases per million [1].

Classification of dystonia distinguishes (1) inherited dystonia, with proven genetic origin, including both isolated dystonias and those associated with heredodegenerative disorders; (2) acquired dystonia, which can be referred to a known cause, including perinatal brain injury, infection, toxins, and vascular events; and (3) idiopathic dystonia, when the cause is unknown [2]. Dystonia can also be described by age of onset (early or late), body distribution (generalized, segmental, multifocal, or focal), temporal pattern, and associated features. Pediatric dystonias are typically generalized, with DYT1 mutations accounting for 80–90% of cases in Ashkenazi Jewish populations and 16–53% of cases in non-Jewish populations. Other pediatric dystonias can be attributed to one of the other known 27 DYT mutations, as well as other heredodegenerative diseases and acquired causes [1].

There are both oral and injectable options for medical therapy, although their efficacy is limited [3]. As botulinum toxin injections are not a feasible option in most pediatric cases with generalized dystonia, surgical therapy assumes a prominent role in cases refractory to medications or when patients are unable to tolerate medications due to side effects. Among surgical treatments of dystonia, deep brain stimulation (DBS) has emerged as a relatively safe and effective procedure. Although the mechanism of action is not entirely clear, it is thought that chronic stimulation disrupts the abnormal function of thalamic and basal ganglia nuclei in dystonia. A major benefit of DBS is that it is reversible and can be used bilaterally without significant risk of cognitive or motor dysfunction, as previously seen in cases treated with pallidotomy [4]. Ideal candidates for DBS have generalized, segmental, or multifocal dystonia that is refractory to medications and are experiencing significant disability due to impairment of motor function or pain affecting quality of life [5]. Shorter duration of disease, young age, and specific genetic conditions (DYT1) are considered predictors of better outcome [6‒8]; thus, genetic testing may be helpful prior to surgery. Factors that may make DBS a less desirable option include age younger than 7 years, low weight, high risk for infection, poor follow-up, and high risk of suicide [9].

Initial case reports and a series of pallidal DBS for dystonia dating back to the early 2000s demonstrated extremely encouraging results, particularly in primary generalized dystonias [10‒13]. Blinded studies comparing pallidal DBS to sham stimulation in isolated generalized and segmental dystonia showed Burke-Fahn-Marsden dystonia rating score (BFMDRS) improvements ranging from 39.3% at 3 months to 54.6% at 12 months [14, 15]. Additional studies have confirmed remarkable short-term benefits in children, albeit with some variability depending on the underlying etiology, in a wide variety of dystonia subtypes (Table 1) [8, 16‒35].

Table 1.

Pediatric dystonias treated with DBS

 Pediatric dystonias treated with DBS
 Pediatric dystonias treated with DBS

In addition to the accuracy of surgical placement for each individual patient (see later), the ability of the neurologist/programmer to set and adjust multiple stimulation parameters through DBS programming is crucial to optimal clinical outcomes [36]. Most clinicians prefer activating one or two ventral contacts with monopolar stimulation [36], a choice supported by multiple clinical series in adults as well as research based on calculation of effective volumes of tissue activation. These have shown that stimulation of the ventroposterior globus pallidus internus (GPi) is associated with the best motor outcomes [37‒40]. While initial case series have reported positive responses with higher pulse widths up to 450 μs and frequencies of 130 Hz and higher [13], these parameters can rapidly deplete the internal pulse generator (IPG) battery. Later studies have shown equal efficacy with lower frequencies [41, 42] and narrower pulse widths [43].

Despite the undisputable efficacy of DBS in the short term, there is limited literature supporting the long-term benefits in the pediatric population. Some studies have shown a persistent [38, 44] or even improved effect [45], but others have suggested the potential for dystonia recurrence [46, 47]. In addition, there is concern about the long-term tolerability of DBS implants. Further analysis is therefore warranted, as pediatric patients will likely live with DBS implants for multiple decades or their entire life. They, and their parents, need to be counseled appropriately on both the expected long-term benefits and possible adverse effects, including hardware complications or neuropsychiatric impact.

Over two decades of experience have codified DBS surgery procedures, with some variations between adult and pediatric patients. Stereotactic surgery for DBS device implantation is typically performed in two parts: first, the stimulating lead is placed into the target of choice, and second, the extension cable and pulse generator are implanted. While a single-stage procedure may be more efficient, it is associated with a higher rate of surgical infection [48]. The target is identified either by estimate coordinates from brain atlases or with direct visualization on imaging, with particular attention to trajectory to avoid lateral ventricles and cortical veins to decrease the risk of hemorrhage [49]. Children with severe dystonia, frequently complicated by developmental delay, are often unable to tolerate awake surgery due to the difficulty cooperating with instructions and risk of involuntary movements while in a stereotactic frame [50, 51]. Therefore, different than adult practices, most DBS implants in pediatric patients are performed under general anesthesia [52]. Alternatively, a combination of dexmedetomidine and propofol or remifentanil and ketamine can be safely used to obtain adequate sedation and analgesia without respiratory depression [53], preserving microelectrode recordings and awake cooperation with intraoperative testing [50]. In those cases where asleep placement is preferred, frame-based stereotactic surgery is performed without microelectrode recordings and confirmed postoperatively with either computed tomography (CT) or magnetic resonance imaging [54, 55]. The downside to this approach is that accuracy becomes dependent uniquely on the frame system [56], in addition to the logistical difficulty of transporting patients between different locations. Alternatively, intraoperative CT images can be obtained and then fused to preoperative MRI to confirm lead placement [57‒59], a procedure possibly limited by the accuracy of the image fusion software [58, 60]. The use of interventional MRI-guided DBS using a skull-mounted aiming device in conjunction with dedicated software, which is independent of physiological testing, showed good accuracy and comparable outcomes in pediatric dystonia [29, 61]. Robot-assisted stereotactic implantation may have even greater accuracy [62].

Optimal targets may vary, particularly for children with acquired dystonia who may have structural lesions within the basal ganglia making standard GPi placement more difficult to visualize or less responsive to DBS [63]. There is no data directly comparing GPi versus subthalamic nucleus (STN) or thalamic stimulation in the pediatric population. STN stimulation demonstrated good outcomes in one pediatric study of 9 patients with isolated dystonia [35]. A phase 1 trial exploring bilateral thalamic DBS targeting the nucleus ventralis intermedius/ventral oral posterior (Vim/Vop) in pediatric patients with acquired dystonia showed outcomes comparable to pallidal stimulation [64]. Temporary implantation of depth electrodes can provide neurophysiological testing of potential target sites prior to permanent insertion [51].

About 1–4 weeks after brain electrode implantation, a second surgery is performed to place the IPG, typically in the chest below the clavicle bone, like a cardiac pacemaker. Implanted brain leads are connected to an extension wire tunneled behind the ear and down the neck to reach the IPG in the chest. About 1 week after IPG placement, to allow for wound healing, a clinician can proceed to perform initial programming using a handheld device to communicate with the IPG and achieve therapeutic stimulation.

Several innovations have advanced the DBS field over the past few years. Directional leads have been created to improve current steering, using segmented contacts designed to prevent current spread to nearby structures, possibly associated with side effects [65]. There is limited data on the use of directional leads in dystonia, but studies exploring the use of computational VTA models have demonstrated potential benefit [66]. Sensing technologies able to measure local field potential (LFP) recordings are also being studied. LFP theta band activity within the GPi seems to correspond to dystonia severity [67] and is maximal at optimal contacts [68]. In the future, clinicians may be able to use this information to readily identify the best DBS settings or create a closed-loop or adaptive neuromodulatory algorithm. New visualization tools provide 3D reconstructions of lead placement using patient-specific anatomical plates derived by MRI and CT imaging [69]. Anatomical visualization will likely simplify programming by guiding the choice of active electrodes and size of the electrical field, in addition to help with troubleshooting when lack of benefit or intolerable side effects ensue. Lastly, technology that allows remote DBS programming via telemedicine was recently approved by the FDA [69], a development that will improve access to DBS treatment in rural areas.

Search Strategy

We conducted a literature search using PubMed for case reports, case series, reviews, or clinical trials prior to April 1, 2021, reporting data on pediatric dystonia patients who underwent DBS implantation (age <21 years at surgery). We used the following search terms were used in combination to identify potential articles: “pediatric” OR “children,” and “dystonia,” and “deep brain stimulation.” Abstracts and full-text articles were reviewed. The references of each article were further reviewed for additional studies that were not captured by the original search. A total of 217 studies were retrieved. Additional search phrase “long term” was used to capture articles that discussed long-term motor, neuropsychiatric, and/or quality of life outcomes, as well as adverse events. This yielded 44 articles, 20 of which included individual patient data demonstrating at least one patient who had post-DBS follow-up of at least 5 years and BFMDRS motor scores at last follow-up. Five articles discussed long-term outcomes after DBS placement for status dystonicus.

Inherited Dystonia

Without Central Nervous System Pathology

Patients with inherited dystonia without central nervous system pathology have been historically preferred candidates for DBS due to the possible expectation of complete symptom resolution in the absence of an underlying structural lesion or degeneration. The most common gene mutation found in childhood-onset generalized dystonia is DYT1, which is the result of a GAG deletion in the gene encoding torsin A. It is inherited in an autosomal dominant pattern with 30–40% penetrance as well as variable phenotypic expression [70]. Multiple studies have shown a robust response to GPi DBS in pediatric patients with DYT1, ranging from 40.5%–88.3% as measured by mean BFMDRS motor score and 50%–76.8% as measured by BFMDRS disability score [7, 18‒20, 26, 71‒74].

DYT6 dystonia is caused by mutations of the THAP1 gene and is inherited in an autosomal dominant fashion with about 60% penetrance. Symptom onset is in the cranio-cervical region in about half of patients, and in the upper extremities in other patients [75]. While experience with this population is more limited, it appears that patients with DYT6 dystonia experience a generally good but more modest and less sustained response to pallidal DBS as compared to DYT1 patients [76‒78].

Myoclonus-dystonia (DYT11) is a syndrome characterized by both dystonia and myoclonic jerks, associated with mutations or deletions in the epsilon-sarcoglycan gene in about 30–50% of cases [79]. Most of the literature regarding DBS outcomes in patients with DYT11 myoclonus-dystonia is based on relatively small case series, but meta-analyses have demonstrated substantially positive outcomes in pediatric cohorts, with average and median motor improvements of dystonic components of around 70% [80, 81]. Improvement in myoclonus has also been documented [30, 82]. A combination of pallidal and thalamic stimulation has also been explored and has shown sustained benefit of motor symptoms in DYT11 cases [83].

Several case reports and small series have described DBS outcomes in pediatric patients affected by the newly identified DYT28 dystonia, caused by a mutation in the KMT2B gene. The spectrum of clinical manifestations includes generalized dystonia, in most cases involving the lower limbs at onset with later generalization, and unlike DYT1, spreads to include the larynx and oromandibular region as well [33]. In one series of adult and pediatric patients, 8 patients who underwent DBS had a median 38.5% improvement of BFMDRS motor score [33]. Another study with 15 adult and pediatric patients showed >30% motor improvement at 1 year in 8 patients, but this was sustained only in 5 patients. Dystonia improvement was maintained for trunk and neck more than oromandibular regions [84].

With Central Nervous System Pathology

Despite the presence of an active neurodegenerative process and thus a reduced expectation for complete and sustained reversal of deficits, dystonias with central nervous system pathology have been targeted due to the lack of other treatment options. Most information about DBS outcomes is available for neurodegeneration with brain iron accumulation, which describes multiple degenerative diseases characterized by various movement disorders and cognitive decline, resulting in severe disability and shortened survival. The most common form is pantothenate kinase-associated neurodegeneration (PKAN), an autosomal recessive disorder caused by PANK2 gene mutations. While it can have variable phenotypes, the classic form causes childhood dystonia, ataxia, spasticity, parkinsonism, and cognitive impairment [85]. Due to its severity, PKAN has been a target of DBS therapy since the early years of therapy development [86], providing a large caseload with inconsistent outcomes. One meta-analysis noted short-term median improvement in the BFMDRS motor score of 27.7% in 36 pediatric patients with PKAN [80].

Lesch-Nyhan disease is an X-linked recessive disorder caused by mutations in the HPRT1 gene. Decreased hypoxanthine-guanine phosphoribosyl transferase activity causes excessive uric acid accumulation, which results in generalized dystonia, self-injurious behavior, intellectual disability, gout, and nephrolithiasis [87]. This rare and disabling condition has been treated with pallidal DBS in few selected cases, often targeting bilateral anteromedial in addition to posteroventral GPi in order to affect limbic symptoms with the modified stimulation target [34, 88]. A meta-analysis of 4 patients showed a mean of 26.4% improvement in the BFMDRS motor score [80]. Another series of 4 patients showed only a 3.4% mean improvement in BFMDRS motor score, but 2 patients showed >50% improvement in frequency and severity on behavioral scales, with 1 patient being able to return to school. These patients also had significant improvements in other disability and quality-of-life metrics [34].

Acquired Dystonia

Patients with acquired dystonia comprise a heterogeneous group, with multiple etiologies and neurologic deficits. These patients tend to have a more static pathological process than those of heredodegenerative pathology, but frequently present other issues – such as spasticity – that may limit outcome expectations after DBS surgery [5]. Cerebral palsy is the most common indication for DBS in secondary dystonia. Its prevalence is 2 per 1,000 live births [89], and underlying causes include hypoxic ischemic encephalopathy and prematurity. Overall, DBS short-term outcomes show variable benefits, ranging from 9.3% to 28.5% in mean BFMDRS motor score improvement [20, 22, 25, 28, 90, 91].

Idiopathic Dystonia

Many cases of focal or segmental dystonia fall into this category, mostly with adult onset, sporadic or familial occurrence. Patients with idiopathic dystonia have been treated with surgery in a similar fashion to those with DYT1 and other inherited forms of the disease. In pediatric patients without a recognized genetic mutation, those who have an isolated dystonia respond quite well to GPi DBS, with average improvements ranging from 31.7% to 72% as measured by the BFMDRS motor score and 26.4–66.5% as measured by the BFMDRS disability score [18‒20, 26, 73, 74].

In the following sections, we present data relative to long-term motor and neuropsychiatric outcomes of DBS, as well as complications including battery changes. In addition, we will review long-term outcomes after DBS placement for status dystonicus (SD).

Motor Outcomes

We identified 20 articles that included individual data documenting motor outcomes of pallidal and subthalamic stimulation with 5 or more years of follow-up (Table 2). Data was available on a total of 78 individual patients of pediatric age; 43 were male, 34 were female, and 1 was unknown. The mean age at dystonia onset was 7.2 ± 3.3 years and mean age at DBS was 13.1 ± 3.9 years, with an average duration of disease prior to DBS of 6.1 ± 3.9 years. The average length of follow-up for the cases included in this study was 8.5 ± 3.3 years. The vast majority of patients (n = 69) were implanted within the GPi, with 8 patients receiving STN implantation and 1 patient targeted within the ventrolateral posterior nucleus of the thalamus. Dystonia was generalized in 77 patients, with only one focal dystonia [26]. This population included 58 patients with an inherited, isolated dystonia (42 DYT1, 7 DYT6, 7 DYT28, and 2 DYT11, shown in Table 2), 6 patients with heredodegenerative dystonia (4 PKAN and 2 Lesch-Nyhan), 2 patients with an acquired dystonia due to CP, and 12 patients with idiopathic dystonia. The average BFMDRS motor score at baseline was 57.8 ± 23.6 points. The baseline disability score, available in only 42 patients, was 17.8 ± 7.5 points. The mean percentage motor score improvement at last follow-up was 56.7 ± 40.9, with an average percentage disability score improvement of 61.4 ± 35.5%. These results support sustained motor benefit and reduced disability after DBS for dystonia.

Table 2.

Long-term motor outcomes of DBS for pediatric dystonia

 Long-term motor outcomes of DBS for pediatric dystonia
 Long-term motor outcomes of DBS for pediatric dystonia

Differential improvements among the different genetic subtypes of dystonia are shown in Figure 1. Patients with idiopathic, DYT11, and DYT1 dystonia demonstrated the greatest benefit, while patients with cerebral palsy and DYT6 showed moderate benefit, and patients with DYT28, PKAN, and Lesch-Nyhan showed the least long-term benefit. These results are consistent with previous studies with shorter follow-up showing greater benefit in patients with inherited, isolated dystonias and idiopathic dystonias compared to both heredodegenerative and acquired dystonias [80, 92]. Interestingly, the patients with acquired dystonia that emerged from our analysis had better outcomes than previously reported [20, 22, 25, 28, 90, 91], although they were still poorer overall as compared to patients with inherited, isolated dystonia. Poorer outcomes may be attributed to the higher incidence of structural brain damage in these patients, as well as disability due to other neurologic deficits and progressive neurodegeneration [80, 93].

Fig. 1.

BFMDRS motor improvement by dystonia subtype. BFMDRS, Burke-Fahn-Marsden dystonia rating scale; PKAN, pantothenate kinase-associated neurodegeneration.

Fig. 1.

BFMDRS motor improvement by dystonia subtype. BFMDRS, Burke-Fahn-Marsden dystonia rating scale; PKAN, pantothenate kinase-associated neurodegeneration.

Close modal

Analysis of body regions involved by dystonia – available in 37 patients – showed 23 with facial and/or laryngeal involvement, 26 with cervical involvement, 32 with upper extremity involvement, 31 with lower extremity involvement, and 34 with truncal involvement. Out of 33 patients with data regarding region of onset, 18 had a lower extremity, 13 upper extremity, 1 laryngeal, and 1 cervical onset. Data regarding medication changes post-DBS was available for 16 patients, 13 of which (76%) were able to eliminate medications completely, while 3 patients were not. In 13 patients, dystonia spread to new regions post-DBS, including 7 spreads to the face, 4 to the larynx, and 6 to other regions. Given the prevalent spread of dystonia in pediatric patients [94], it is intriguing to notice that 22/35 (62%) of patients did not have spread to other regions after DBS.

There is a lack of data regarding long-term outcome predictors in pediatric dystonia patients that undergo DBS surgery. Overall, in primary generalized dystonia, age at onset [80, 93, 95], shorter disease duration [6‒8, 93, 96] and absence of fixed skeletal deformities are associated with better outcomes [6, 37]. Thus, DBS should be offered early in order to maximize benefit and avoid the development of musculoskeletal deformity, both in primary and secondary dystonia [8, 22]. Truncal and limb dystonia tend to respond better than orolingual symptoms [16, 80]. DBS is associated with a significant decrease in medication requirements and sometimes in complete elimination of dystonia medications [21]. Limited series have reported long-term benefits in pediatric cohorts, at 10 years and beyond [35, 73].

Neuropsychiatric Outcomes

Literature regarding neuropsychiatric and quality of life outcomes in the long term is quite limited. In a STN DBS study including 9 pediatric patients with isolated dystonia and 10 years of follow-up, two reported stimulation-induced cognitive impairment with regard to executive function, one reported anxiety, two reported depression, and one reported weight gain. At the same time, all of them reported a significant improvement in quality of life. Gains included the ability to walk freely without assistance, perform ADLs independently including eating and writing, and function normally with return to school and work [35].

Another study included 2 pediatric patients with myoclonus-dystonia who underwent GPi DBS. Cognitive and quality of life scales were performed at the last follow-up, 5.3 and 5.7 years after implantation. They both had high scores on cognitive testing (MMSE), quality of life scales (SF-36), and anxiety/depression scales (BDI, HADS), with mild functional impairments on the social adjustment scale. One patient did report some mild anxiety, as well as some difficulty with social and physical role functioning, body pain, vitality, and mental health. Ultimately, these quality-of-life scores were similar to those of the general population. Furthermore, they were able to obtain their driver’s licenses as well as pursue higher level education [97].

In a cohort of 37 pediatric patients and adults, quality of life improvements persisted for the past 10 years, with low prevalence of cognitive impairment [98]. Another mixed cohort of 46 patients with a median follow-up of 4 years demonstrated complete elimination of dystonia medications in 61% of patients, and discontinuation of at least 1 class of medication in 91% at last follow-up [38]. A pediatric group with a median follow-up of 8 years demonstrated a decrease in mean daily anticholinergic dose from 29.9 (±35.6 mg) to 3 (±5.1 mg), also without any cognitive decline in MOCA scores at last follow-up [99].

Long-Term Outcomes after SD

SD is characterized by increased severity of dystonia requiring urgent hospital admission, often to an intensive care unit, due to life-threatening complications including bulbar weakness, respiratory failure, and metabolic derangements [100]. SD may occur in both primary and secondary dystonia, and is commonly triggered by infection or medication changes, or an interruption in chronic DBS treatment, although sometimes no precipitating factor may be found [101, 102] Refractory SD cases may require consideration of DBS and it has been argued that DBS should be considered early, particularly in conditions that are highly responsive such as DYT1 dystonia. However, more patients presenting with SD have secondary dystonia rather than primary dystonia [102]. DBS surgery was the most successful strategy in 89 adult and pediatric cases of SD [101]. In one cohort of 58 patients of all ages with SD who received DBS, about 90% of episodes resolved [103]. Interestingly, most patients in both series had secondary dystonia, suggesting that DBS should certainly be considered in all types of dystonia.

Five publications described a total of 9 pediatric patients with 5 or more years of follow-up after bilateral GPi DBS placement for the treatment of SD (shown in Table 3). The median age at time of DBS was 11 years (range 8.2–14.2) with a median of 30 days (range 14–180) after SD onset. The median time to SD resolution after DBS placement was 30 days (range 7–90) and the median follow-up was 96 months. Only 2 patients had isolated dystonia; the remaining seven had secondary or heredodegenerative dystonia. Motor scores were not available for all patients, but all of them had resolution of SD. Two patients maintained improvements in BFMDRS motor and disability scores with long-term follow-up. Two patients had initial motor improvements post-DBS but ultimately worsened compared to baseline at last follow-up. One patient gained the ability to walk independently 2 years post-DBS.

Table 3.

Long-term outcomes in status dystonicus

 Long-term outcomes in status dystonicus
 Long-term outcomes in status dystonicus

Battery Changes

One particular risk in children when considering DBS is that they will likely require many battery changes over their lifetime, which may result in a higher risk of surgical complications compared to adults [104]. The mean battery life was 3.1 years in a cohort of children and adults with 9 years of follow-up [72]. The development of rechargeable IPGs has made this issue less important. Rechargeable devices have been shown to be well tolerated in children, with a low complication rate [105].

Adverse Effects

Adverse effects associated with DBS therapy are typically classified into three categories: surgical, hardware-, and stimulation-related. Typical short-term adverse events include post-op wounds or hardware infections. Risk of infection tends to be higher in the pediatric population for several reasons, including smaller body habitus, which results in delayed healing of the IPG incision, as well as strain due to severe dystonia which is more common in pediatric patients [38]. However, the frequency of these events decreases significantly over time. Therefore, long-term effects are typically hardware- or stimulation-related [106].

There is limited data regarding long-term adverse events in pediatric DBS patients. One study reported adverse events associated with DBS ranging from 1 to 15 years (65.8 months on average) after surgery in 42 patients, the majority of which were hardware-related. A total of 42 adverse events were described in 21 patients, 35 of which required surgical intervention. These included 6 accidental arrests of the IPG, 14 unscheduled IPG replacements due to technical defect or dislocation (after a mean of 73.7 months), 14 lead extension replacements due to high impedances, lead fracture or migration, shortening due to growth, or discomfort or pain (after a mean of 62.6 months), and 7 DBS system removals due to high impedances, dislocation, or malposition of the DBS electrode (after a mean of 56.6 months) [107]. While interruptions in stimulation have been associated with motor deterioration and even the development of SD [101, 102], there have been several reports of sustained relief despite prolonged interruption [108‒110]. Other limited reports of late adverse events include lead migration into the temporal lobe causing seizures at 7 years post-op, as well as electrode infection requiring removal and reimplantation at 9 years [26, 77]. Early studies suggested that lead fractures, particularly along the course of the extension cables, were more frequent in dystonia patients than in other movement disorder patients [12]. Later studies did not confirm this finding, although changes in surgical technique (i.e., the connector being placed above the mastoid rather than below) may have contributed to the reduction in lead fractures [37, 46, 111].

Manifestations of parkinsonism, including bradykinesia and freezing of gait, have been described after chronic pallidal stimulation for dystonia [112‒114] and may resolve upon using more dorsal contacts [113]. They increase in frequency with age, particularly after the fourth decade [98] and are therefore quite rare in the pediatric population. However, one study in DYT28 pediatric patients treated with GPi DBS reported freezing of gait at 3–6 years post-DBS [84]. In addition, stimulation-induced speech abnormalities, including dysarthria, dysphonia, and stuttering, are frequently reported [106]. Speech difficulties do complicate DBS therapy in the pediatric population, depending on stimulation intensity, likely related to activation of fibers of the internal capsule [107, 115].

Our systematic review of the literature describing long-term DBS outcomes in pediatric dystonia delivers an encouraging message, as motor and quality of life benefits of DBS for dystonia are maintained 5 or more years after implantation, with minimal cognitive or psychiatric deterioration. Serious complications are rare and the development of rechargeable IPGs has made frequent battery replacement less of an issue. Despite tremendous advances in genetic and molecular studies, which may ultimately result in a cure for dystonia, these results confirm the leading role of DBS in the current treatment options for most cases of generalized, medication-resistant, and disabling dystonia.

C.M. has no conflicts of interest to declare. M.T. received consultation fees from Abbot, Boston Scientific, and Medtronic. None of these relationships had any influence on the content of this review.

M.T. received funding from the Caron and Steven D. Broidy Chair in Movement Disorders.

C.M.: literature review and initial manuscript draft. M.T.: literature review and manuscript editing.

1.
Fernández-Alvarez
E
,
Nardocci
N
.
Update on pediatric dystonias: etiology, epidemiology, and management
.
Degener Neurol Neuromuscul Dis
.
2012
;
2
:
29
.
2.
Albanese
A
,
Bhatia
K
,
Bressman
SB
,
DeLong
MR
,
Fahn
S
,
Fung
V
, et al
.
Phenomenology and classification of dystonia: a consensus update
.
Mov Disord
.
2013
;
28
:
863
.
3.
Tagliati
M
,
Blatt
K
,
Bressman
S
.
Generalized torsion dystonia
. In:
Noseworthy John
H
,
Martin
D
, editors.
Neurological therapeutics: principles and practice
;
2003
.
4.
Marks
WJ
Jr.
.
Brain surgery for dystonia
. In:
Stacy Mark
A
, editor.
Handbook of dystonia
.
Informa Healthcare
;
2007
. p.
393
401
.
5.
Tagliati
M
,
Shils
J
,
Sun
C
,
Alterman
R
.
Deep brain stimulation for dystonia
.
Expert Rev Med Devices
.
2014
;
1
:
33
41
.
6.
Isaias
IU
,
Alterman
RL
,
Tagliati
M
.
Outcome predictors of pallidal stimulation in patients with primary dystonia: the role of disease duration
.
Brain
.
2008
;
131
:
1895
902
.
7.
Markun
LC
,
Starr
PA
,
Air
EL
,
Marks
WJ
,
Volz
MM
,
Ostrem
JL
.
Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia
.
Neurosurgery
.
2012
;
71
:
325
30
.
8.
Lumsden
DE
,
Kaminska
M
,
Gimeno
H
,
Tustin
K
,
Baker
L
,
Perides
S
, et al
.
Proportion of life lived with dystonia inversely correlates with response to pallidal deep brain stimulation in both primary and secondary childhood dystonia
.
Dev Med Child Neurol
.
2013
;
55
:
567
74
.
9.
Larsh
T
,
Wu
SW
,
Vadivelu
S
,
Grant
GA
,
O’Malley
JA
.
Deep brain stimulation for pediatric dystonia
.
Semin Pediatr Neurol
.
2021
;
38
:
100896
.
10.
Tronnier Volker
M
,
Fogel
W
.
Pallidal stimulation for generalized dystonia: report of three cases
.
J Neurosurg
.
2000
;
92
:
453
6
.
11.
Bereznai
B
,
Steude
U
,
Seelos
K
,
Bötzel
K
.
Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: a clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia
.
Mov Disord
.
2002
;
17
:
138
44
.
12.
Yianni
J
,
Bain
P
,
Giladi
N
,
Auca
M
,
Gregory
R
,
Joint
C
, et al
.
Globus pallidus internus deep brain stimulation for dystonic conditions: a prospective audit
.
Mov Disord
.
2003
;
18
:
436
42
.
13.
Coubes
P
,
Roubertie
A
,
Vayssiere
N
,
Hemm
S
,
Echenne
B
.
Treatment of DYT1-generalised dystonia by stimulation of the internal globus pallidus
.
Lancet
.
2000
;
355
:
2220
1
.
14.
Vidailhet
M
,
Vercueil
L
,
Houeto
JL
,
Krystkowiak
P
,
Benabid
AL
,
Cornu
P
, et al
.
Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia
.
N Engl J Med
.
2005
;
352
:
459
67
.
15.
Kupsch
A
,
Benecke
R
,
Müller
J
,
Trottenberg
T
,
Schneider
GH
,
Poewe
W
, et al
.
Pallidal deep-brain stimulation in primary generalized or segmental dystonia
.
N Engl J Med
.
2006
;
355
:
1978
90
.
16.
Zorzi
G
,
Marras
C
,
Nardocci
N
,
Franzini
A
,
Chiapparini
L
,
Maccagnano
E
, et al
.
Stimulation of the globus pallidus internus for childhood-onset dystonia
.
Mov Disord
.
2005
;
20
:
1194
200
.
17.
Alterman
RL
,
Tagliati
M
.
Deep brain stimulation for torsion dystonia in children
.
Childs Nerv Syst
.
2007
;
23
:
1033
40
.
18.
Parr
JR
,
Green
AL
,
Joint
C
,
Andrew
M
,
Gregory
RP
,
Scott
RB
, et al
.
Deep brain stimulation in childhood: an effective treatment for early onset idiopathic generalised dystonia
.
Arch Dis Child
.
2007
;
92
:
708
11
.
19.
Borggraefe
I
,
Mehrkens
JH
,
Telegravciska
M
,
Berweck
S
,
Bötzel
K
,
Heinen
F
.
Bilateral pallidal stimulation in children and adolescents with primary generalized dystonia: report of six patients and literature-based analysis of predictive outcomes variables
.
Brain Dev
.
2010
;
32
:
223
8
.
20.
Air
EL
,
Ostrem
JL
,
Sanger
TD
,
Starr
PA
.
Deep brain stimulation in children: experience and technical pearls
.
J Neurosurg Pediatr
.
2011
;
8
:
566
74
.
21.
Haridas
A
,
Tagliati
M
,
Osborn
I
,
Isaias
I
,
Gologorsky
Y
,
Bressman
SB
, et al
.
Pallidal deep brain stimulation for primary dystonia in children
.
Neurosurgery
.
2011
;
68
:
738
43
.
22.
Marks
WA
,
Honeycutt
J
,
Acosta
F
,
Reed
M
,
Bailey
L
,
Pomykal
A
, et al
.
Dystonia due to cerebral palsy responds to deep brain stimulation of the globus pallidus internus
.
Mov Disord
.
2011
;
26
:
1748
51
.
23.
Ghosh
PS
,
Machado
AG
,
Deogaonkar
M
,
Ghosh
D
.
Deep brain stimulation in children with dystonia: experience from a tertiary care center
.
Pediatr Neurosurg
.
2012
;
48
:
146
51
.
24.
Gimeno
H
,
Tustin
K
,
Selway
R
,
Lin
JP
.
Beyond the Burke-Fahn-Marsden dystonia rating scale: deep brain stimulation in childhood secondary dystonia
.
Eur J Paediatr Neurol
.
2012
;
16
:
501
8
.
25.
Marks
W
,
Bailey
L
,
Reed
M
,
Pomykal
A
,
Mercer
M
,
Macomber
D
, et al
.
Pallidal stimulation in children: comparison between cerebral palsy and DYT1 dystonia
.
Child Neurol
.
2013
;
28
:
840
8
.
26.
Petrossian
MT
,
Paul
LR
,
Multhaupt-Buell
TJ
,
Eckhardt
C
,
Hayes
MT
,
Duhaime
AC
, et al
.
Pallidal deep brain stimulation for dystonia: a case series
.
Neurosurg Pediatr
.
2013
;
12
:
582
7
.
27.
Gimeno
H
,
Tustin
K
,
Lumsden
D
,
Ashkan
K
,
Selway
R
,
Lin
JP
.
Evaluation of functional goal outcomes using the Canadian Occupational Performance Measure (COPM) following Deep Brain Stimulation (DBS) in childhood dystonia
.
Eur J Paediatr Neurol
.
2014
;
18
:
308
16
.
28.
Keen
JR
,
Przekop
A
,
Olaya
JE
,
Zouros
A
,
Hsu
FP
.
Deep brain stimulation for the treatment of childhood dystonic cerebral palsy
.
J Neurosurg Pediatr
.
2014
;
14
:
585
93
.
29.
Starr
PA
,
Markun
LC
,
Larson
PS
,
Volz
MM
,
Martin
AJ
,
Ostrem
JL
.
Interventional MRI-guided deep brain stimulation in pediatric dystonia: first experience with the ClearPoint system
.
J Neurosurg Pediatr
.
2014
;
14
:
400
8
.
30.
Candela
S
,
Vanegas
MI
,
Darling
A
,
Ortigoza-Escobar
JD
,
Alamar
M
,
Muchart
J
, et al
.
Frameless robot-assisted pallidal deep brain stimulation surgery in pediatric patients with movement disorders: precision and short-term clinical results
.
Neurosurg Pediatr
.
2018
;
22
:
416
25
.
31.
Kawarai
T
,
Miyamoto
R
,
Nakagawa
E
,
Koichihara
R
,
Sakamoto
T
,
Mure
H
, et al
.
Phenotype variability and allelic heterogeneity in KMT2B-Associated disease
.
Parkinsonism Relat Dis
.
2018
;
52
:
55
61
.
32.
Koy
A
,
Cirak
S
,
Gonzalez
V
,
Becker
K
,
Roujeau
T
,
Milesi
C
, et al
.
Deep brain stimulation is effective in pediatric patients with GNAO1 associated severe hyperkinesia
.
J Neurol Sci
.
2018
;
391
:
31
9
.
33.
Carecchio
M
,
Invernizzi
F
,
Gonzàlez-Latapi
P
,
Panteghini
C
,
Zorzi
G
,
Romito
L
, et al
.
Frequency and phenotypic spectrum of KMT2B dystonia in childhood: a Single-Center Cohort Study
.
Mov Disord
.
2019
;
34
:
1516
27
.
34.
Tambirajoo
K
,
Furlanetti
L
,
Hasegawa
H
,
Raslan
A
,
Gimeno
H
,
Lin
JP
, et al
.
Deep brain stimulation of the internal pallidum in Lesch-Nyhan syndrome: clinical outcomes and connectivity analysis
.
Neuromodulation
.
2021
;
24
:
380
91
.
35.
Xu
W
,
Li
H
,
Zhang
C
,
Sun
B
,
Wu
Y
,
Li
D
.
Subthalamic nucleus stimulation in pediatric isolated dystonia: a 10-year follow-up
.
Can J Neurol Sci
.
2020
;
47
:
328
35
.
36.
Malatt
C
,
Tagliati
M
.
Managing dystonia patients treated with deep brain stimulation
. 3rd ed. In:
Jill
O
,
Marks William
J
, editors.
Deep brain stimulation management
.
Cambridge
:
Cambridge University Press
. (In press).
37.
Isaias
IU
,
Alterman
RL
,
Tagliati
M
.
Deep brain stimulation for primary generalized dystonia: long-term outcomes
.
Arch Neurol
.
2009
;
66
:
465
70
.
38.
Panov
F
,
Gologorsky
Y
,
Connors
G
,
Tagliati
M
,
Miravite
J
,
Alterman
RL
.
Deep brain stimulation in DYT1 dystonia: a 10-year experience
.
Neurosurgery
.
2013
;
73
:
86
93
.
39.
Cheung
T
,
Noecker
AM
,
Alterman
RL
,
McIntyre
CC
,
Tagliati
M
.
Defining a therapeutic target for pallidal deep brain stimulation for dystonia
.
Ann Neurol
.
2014
;
76
:
22
30
.
40.
Reich
MM
,
Horn
A
,
Lange
F
,
Roothans
J
,
Paschen
S
,
Runge
J
, et al
.
Probabilistic mapping of the antidystonic effect of pallidal neurostimulation: a Multicentre Imaging Study
.
Brain
.
2019
;
142
:
1386
98
.
41.
Kupsch
A
,
Kuehn
A
,
Klaffke
S
,
Meissner
W
,
Harnack
D
,
Winter
C
, et al
.
Deep brain stimulation in dystonia
.
J Neurol
.
2003
;
250
(
Suppl 1
):
I47
52
.
42.
Alterman
RL
,
Miravite
J
,
Weisz
D
,
Shils
JL
,
Bressman
SB
,
Tagliati
M
.
Sixty hertz pallidal deep brain stimulation for primary torsion dystonia
.
Neurology
.
2007
;
69
:
681
8
.
43.
Vercueil
L
,
Houeto
JL
,
Krystkowiak
P
,
Lagrange
C
,
Cassim
F
,
Benazzouz
A
, et al
.
Effects of pulse width variations in pallidal stimulation for primary generalized dystonia
.
J Neurol
.
2007
;
254
:
1533
7
.
44.
Tsuboi
T
,
Jabarkheel
Z
,
Foote
KD
,
Okun
MS
,
Wagle Shukla
A
.
Importance of the initial response to GPi deep brain stimulation in dystonia: a Nine Year Quality of Life Study
.
Parkinsonism Relat Disord
.
2019
;
64
:
249
55
.
45.
Coubes
P
,
Cif
L
,
El Fertit
H
,
Hemm
S
,
Vayssiere
N
,
Serrat
S
, et al
.
Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results
.
J Neurosurg
.
2004
;
101
:
189
94
.
46.
Cersosimo
MG
,
Raina
GB
,
Piedimonte
F
,
Antico
J
,
Graff
P
,
Micheli
FE
.
Pallidal surgery for the treatment of primary generalized dystonia: long-term follow-up
.
Clin Neurol Neurosurg
.
2008
;
110
:
145
50
.
47.
Tsuboi
T
,
Cif
L
,
Coubes
P
,
Ostrem
JL
,
Romero
DA
,
Miyagi
Y
, et al
.
Secondary worsening following DYT1 dystonia deep brain stimulation: a multi-country cohort
.
Front Hum Neurosci
.
2020
;
14
:
242
.
48.
Marks
WA
,
Acord
S
,
Bailey
L
,
Honeycutt
J
.
Neuromodulation in childhood onset dystonia: evolving role of deep brain stimulation
.
Curr Phys Med Rehabil Rep
.
2020
;
88
(
2
):
37
43
.
49.
Starr
PA
,
Bejjani
P
,
Lozano
AM
,
Metman
LV
,
Hariz
MI
.
Stereotactic techniques and perioperative management of DBS in dystonia
.
Mov Disord
.
2011
;
26
(
Suppl 1
):
S23
30
.
50.
Hippard
HK
,
Watcha
M
,
Stocco
AJ
,
Curry
D
.
Preservation of microelectrode recordings with non-GABAergic drugs during deep brain stimulator placement in children
.
J Neurosurg Pediatr
.
2014
;
14
:
279
86
.
51.
Sanger
TD
,
Liker
M
,
Arguelles
E
,
Deshpande
R
,
Maskooki
A
,
Ferman
D
, et al
.
Pediatric deep brain stimulation using awake recording and stimulation for target selection in an inpatient neuromodulation monitoring unit
.
Brain Sci
.
2018
;
8
:
135
.
52.
Kamel
WA
,
Majumdar
P
,
Matis
G
,
Fenoy
AJ
,
Balakrishnan
S
,
Zirh
AT
, et al
.
Surgical management for dystonia: efficacy of deep brain stimulation in the long term
.
Neurol Int
.
2021
;
13
:
371
.
53.
Sebeo
J
,
Deiner
SG
,
Alterman
RL
,
Osborn
IP
.
Anesthesia for pediatric deep brain stimulation
.
Anesthesiol Res Pract
.
2010
;
2010
:
401419
.
54.
Vayssiere
N
,
Hemm
S
,
Zanca
M
,
Picot
MC
,
Bonafe
A
,
Cif
L
, et al
.
Magnetic resonance imaging stereotactic target localization for deep brain stimulation in dystonic children
.
J Neurosurg
.
2000
;
93
:
784
90
.
55.
Maldonado
IL
,
Roujeau
T
,
Cif
L
,
Gonzalez
V
,
El-Fertit
H
,
Vasques
X
, et al
.
Magnetic resonance-based deep brain stimulation technique: a series of 478 consecutive implanted electrodes with no perioperative intracerebral hemorrhage
.
Neurosurgery
.
2009
;
65
:
196
201
.
56.
Maciunas
RJ
,
Galloway
RL
,
Latimer
JW
.
The application accuracy of stereotactic frames
.
Neurosurgery
.
1994
;
35
:
682
5
.
57.
Burchiel
KJ
,
McCartney
S
,
Lee
A
,
Raslan
AM
.
Accuracy of deep brain stimulation electrode placement using intraoperative computed tomography without microelectrode recording
.
J Neurosurg
.
2013
;
119
:
301
6
.
58.
Mirzadeh
Z
,
Chapple
K
,
Lambert
M
,
Dhall
R
,
Ponce
FA
.
Validation of CT-MRI fusion for intraoperative assessment of stereotactic accuracy in DBS surgery
.
Mov Disord
.
2014
;
29
:
1788
95
.
59.
Li
H
,
Wang
T
,
Zhang
C
,
Su
D
,
Lai
Y
,
Sun
B
, et al
.
Asleep deep brain stimulation in patients with isolated dystonia: stereotactic accuracy, efficacy, and safety
.
Neuromodulation
.
2021
;
24
:
272
8
.
60.
Thani
NB
,
Bala
A
,
Swann
GB
,
Lind
CR
.
Accuracy of postoperative computed tomography and magnetic resonance image fusion for assessing deep brain stimulation electrodes
.
Neurosurgery
.
2011
;
69
:
207
14
.
61.
Segar
DJ
,
Tata
N
,
Harary
M
,
Hayes
MT
,
Cosgrove
GR
.
Asleep deep brain stimulation with intraoperative magnetic resonance guidance: a single-institution experience
.
J Neurosurg
.
2021
:
136
(
3
):
699
708
.
62.
Furlanetti
L
,
Ellenbogen
J
,
Gimeno
H
,
Ainaga
L
,
Narbad
V
,
Hasegawa
H
, et al
.
Targeting accuracy of robot-assisted deep brain stimulation surgery in childhood-onset dystonia: a single-center prospective cohort analysis of 45 consecutive cases
.
J Neurosurg Pediatr
.
2021
;
27
:
677
87
.
63.
Lumsden
DE
,
Kaminska
M
,
Ashkan
K
,
Selway
R
,
Lin
JP
.
Deep brain stimulation for childhood dystonia: is “where” as important as in “whom”
.
Eur J Paediatr Neurol
.
2017
;
21
:
176
84
.
64.
San Luciano
M
,
Robichaux-Viehoever
A
,
Dodenhoff
KA
,
Gittings
ML
,
Viser
AC
,
Racine
CA
, et al
.
Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial
.
J Neurosurg Pediatr
.
2020
;
27
:
203
12
.
65.
Steigerwald
F
,
Matthies
C
,
Volkmann
J
.
Directional deep brain stimulation
.
Neurotherapeutics
.
2019
;
16
:
100
4
.
66.
Zhang
S
,
Tagliati
M
,
Pouratian
N
,
Cheeran
B
,
Ross
E
,
Pereira
E
.
Steering the volume of tissue activated with a directional deep brain stimulation lead in the globus pallidus pars interna: a Modeling Study with heterogeneous tissue properties
.
Front Comput Neurosci
.
2020
;
14
:
561180
.
67.
Scheller
U
,
Lofredi
R
,
van Wijk
B
,
Saryyeva
A
,
Krauss
JK
,
Schneider
GH
, et al
.
Pallidal low-frequency activity in dystonia after cessation of long-term deep brain stimulation
.
Mov Disord
.
2019
;
34
:
1734
9
.
68.
Neumann
WJ
,
Horn
A
,
Ewert
S
,
Huebl
J
,
Brücke
C
,
Slentz
C
, et al
.
A localized pallidal physiomarker in cervical dystonia
.
Ann Neurol
.
2017
;
82
:
912
24
.
69.
Merola
A
,
Singh
J
,
Reeves
K
,
Changizi
B
,
Goetz
S
,
Rossi
L
, et al
.
New frontiers for deep brain stimulation: directionality, sensing technologies, remote programming, robotic stereotactic assistance, asleep procedures, and connectomics
.
Front Neurol
.
2021
;
12
:
1149
.
70.
Bressman
SB
.
Dystonia: phenotypes and genotypes
.
Rev Neurol
.
2003
;
159
:
849
.
71.
Magariños-Ascone
CM
,
Regidor
I
,
Gómez-Galán
M
,
Cabañes-Martínez
L
,
Figueiras-Méndez
R
.
Deep brain stimulation in the globus pallidus to treat dystonia: electrophysiological characteristics and 2 years’ follow-up in 10 patients
.
Neuroscience
.
2008
;
152
:
558
71
.
72.
Cif
L
,
Vasques
X
,
Gonzalez
V
,
Ravel
P
,
Biolsi
B
,
Collod-Beroud
G
, et al
.
Long-term follow-up of DYT1 dystonia patients treated by deep brain stimulation: an Open-Label Study
.
Mov Disord
.
2010
;
25
:
289
99
.
73.
Krause
P
,
Lauritsch
K
,
Lipp
A
,
Horn
A
,
Weschke
B
,
Kupsch
A
, et al
.
Long-term results of deep brain stimulation in a cohort of eight children with isolated dystonia
.
J Neurol
.
2016
;
263
:
2319
26
.
74.
Scaratti
C
,
Zorzi
G
,
Guastafierro
E
,
Leonardi
M
,
Covelli
V
,
Toppo
C
, et al
.
Long term perceptions of illness and self after deep brain stimulation in pediatric dystonia: a narrative research
.
Eur J Paediatr Neurol
.
2020
;
26
:
61
7
.
75.
Saunders-Pullman
R
,
Raymond
D
,
Senthil
G
,
Kramer
P
,
Ohmann
E
,
Deligtisch
A
, et al
.
Narrowing the DYT6 dystonia region and evidence for locus heterogeneity in the Amish-Mennonites
.
Am J Med Genetics A
.
2007
;
143A
:
2098
105
.
76.
Panov
F
,
Tagliati
M
,
Ozelius
LJ
,
Fuchs
T
,
Gologorsky
Y
,
Cheung
T
, et al
.
Pallidal deep brain stimulation for DYT6 dystonia
.
J Neurol Neurosurg Psychiatry
.
2012
;
83
:
182
7
.
77.
Krause
P
,
Brüggemann
N
,
Völzmann
S
,
Horn
A
,
Kupsch
A
,
Schneider
GH
, et al
.
Long-term effect on dystonia after pallidal deep brain stimulation (DBS) in three members of a family with a THAP1 mutation
.
J Neurol
.
2015
;
262
:
2739
44
.
78.
Danielsson
A
,
Carecchio
M
,
Cif
L
,
Koy
A
,
Lin
JP
,
Solders
G
, et al
.
Pallidal deep brain stimulation in DYT6 dystonia: clinical outcome and predictive factors for motor improvement
.
J Clin Med
.
2019
;
8
:
2163
.
79.
Rachad
L
,
El Kadmiri
N
,
Slassi
I
,
El Otmani
H
,
Nadifi
S
.
Genetic aspects of myoclonus-dystonia syndrome (MDS)
.
Mol Neurobiol
.
2017
;
54
:
939
42
.
80.
Elkaim
LM
,
Alotaibi
NM
,
Sigal
A
,
Alotaibi
HM
,
Lipsman
N
,
Kalia
SK
, et al
.
Deep brain stimulation for pediatric dystonia: a meta-analysis with individual participant data
.
Dev Med Child Neurol
.
2019
;
61
:
49
56
.
81.
Wang
X
,
Yu
X
.
Deep brain stimulation for myoclonus dystonia syndrome: a meta-analysis with individual patient data
.
Neurosurg Rev
.
2021
;
44
(
1
):
451
62
.
82.
Besa Lehmann
V
,
Rosenbaum
M
,
Bulman
DE
,
Read
T
,
Verhagen Metman
L
.
A case report of myoclonus-dystonia with isolated myoclonus phenotype and novel mutation successfully treated with deep brain stimulation
.
Neurol Ther
.
2020
;
9
:
187
91
.
83.
Krause
P
,
Koch
K
,
Gruber
D
,
Kupsch
A
,
Gharabaghi
A
,
Schneider
GH
, et al
.
Long-term effects of pallidal and thalamic deep brain stimulation in myoclonus dystonia
.
Eur J Neurol
.
2021
;
28
:
1566
73
.
84.
Cif
L
,
Demailly
D
,
Lin
JP
,
Barwick
KE
,
Sa
M
,
Abela
L
, et al
.
KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation
.
Brain
.
2020
;
143
:
3242
61
.
85.
di Meo
I
,
Tiranti
V
.
Classification and molecular pathogenesis of NBIA syndromes
.
Eur J Paediatr Neurol
.
2018
;
22
:
272
84
.
86.
Castelnau
P
,
Cif
L
,
Valente
EM
,
Vayssiere
N
,
Hemm
S
,
Gannau
A
, et al
.
Pallidal stimulation improves pantothenate kinase–associated neurodegeneration
.
Ann Neurol
.
2005
;
57
:
738
41
.
87.
Fu
R
,
Ceballos-Picot
I
,
Torres
RJ
,
Larovere
LE
,
Yamada
Y
,
Nguyen
KV
, et al
.
Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder
.
Brain
.
2014
;
137
:
1282
303
.
88.
Cif
L
,
Biolsi
B
,
Gavarini
S
,
Saux
A
,
Robles
SG
,
Tancu
C
, et al
.
Antero-ventral internal pallidum stimulation improves behavioral disorders in Lesch-Nyhan disease
.
Mov Disord
.
2007
;
22
:
2126
9
.
89.
Winter
S
,
Autry
A
,
Boyle
C
,
Yeargin-Allsopp
M
.
Trends in the prevalence of cerebral palsy in a Population-Based Study
.
Pediatrics
.
2002
;
110
:
1220
5
.
90.
Olaya
JE
,
Christian
E
,
Ferman
D
,
Luc
Q
,
Krieger
MD
,
Sanger
TD
, et al
.
Deep brain stimulation in children and young adults with secondary dystonia: the children’s hospital Los Angeles experience
.
Neurosurgical Focus
.
2013
;
35
:
E7
.
91.
Koy
A
,
Weinsheimer
M
,
Pauls
KA
,
Kühn
A
,
Krause
P
,
Huebl
J
, et al
.
German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM)
.
Eur J Paediatr Neurol
.
2017
;
21
:
136
46
.
92.
Hale
AT
,
Monsour
MA
,
Rolston
JD
,
Naftel
RP
,
Englot
DJ
.
Deep brain stimulation in pediatric dystonia: a systematic review
.
Neurosurg Rev
.
2020
;
43
:
873
80
.
93.
Artusi
CA
,
Dwivedi
A
,
Romagnolo
A
,
Bortolani
S
,
Marsili
L
,
Imbalzano
G
, et al
.
Differential response to pallidal deep brain stimulation among monogenic dystonias: systematic review and meta-analysis
.
J Neurol Neurosurg Psychiatry
.
2020
;
91
:
426
33
.
94.
Ozelius
LJ
,
Bressman
SB
.
Genetic and clinical features of primary torsion dystonia
.
Neurobiol Dis
.
2011
;
42
:
127
35
.
95.
Moro
E
,
LeReun
C
,
Krauss
JK
,
Albanese
A
,
Lin
JP
,
Walleser Autiero
S
, et al
.
Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis
.
Eur J Neurol
.
2017
;
24
:
552
60
.
96.
Wu
YS
,
Ni
LH
,
Fan
RM
,
Yao
MY
.
Meta-regression analysis of the long-term effects of pallidal and subthalamic deep brain stimulation for the treatment of isolated dystonia
.
World Neurosurg
.
2019
;
129
:
e409
16
.
97.
Kosutzka
Z
,
Tisch
S
,
Bonnet
C
,
Ruiz
M
,
Hainque
E
,
Welter
ML
, et al
.
Long-term GPi-DBS improves motor features in myoclonus-dystonia and enhances social adjustment
.
Mov Disord
.
2019
;
34
:
87
94
.
98.
Hogg
E
,
During
E
,
Tan
EE
,
Athreya
K
,
Eskenazi
J
,
Wertheimer
J
, et al
.
Sustained quality-of-life improvements over 10 years after deep brain stimulation for dystonia
.
Mov Disord
.
2018
;
33
:
1160
7
.
99.
Ramezani Ghamsari
M
,
Ghourchian
S
,
Emamikhah
M
,
Safdarian
M
,
Shahidi
G
,
Parvaresh
M
, et al
.
Long term follow-up results of deep brain stimulation of the Globus pallidus interna in pediatric patients with DYT1-positive dystonia
.
Clin Neurol Neurosurg
.
2021
:
201
:
106449
.
100.
Manji
H
,
Howard
RS
,
Miller
DH
,
Hirsch
NP
,
Carr
L
,
Bhatia
K
, et al
.
Status dystonicus: the syndrome and its management
.
Brain
.
1998
;
121
(
Pt 2
):
243
52
.
101.
Fasano
A
,
Ricciardi
L
,
Bentivoglio
AR
,
Canavese
C
,
Zorzi
G
,
Petrovic
I
, et al
.
Status dystonicus: predictors of outcome and progression patterns of underlying disease
.
Mov Disord
.
2012
;
27
:
783
8
.
102.
Lumsden
DE
,
King
MD
,
Allen
NM
.
Status dystonicus in childhood
.
Curr Opin Pediatr
.
2017
;
29
:
674
82
.
103.
Nerrant
E
,
Gonzalez
V
,
Milesi
C
,
Vasques
X
,
Ruge
D
,
Roujeau
T
, et al
.
Deep brain stimulation treated dystonia-trajectory via status dystonicus
.
Mov Disord
.
2018
;
33
:
1168
73
.
104.
DiFrancesco
MF
,
Halpern
CH
,
Hurtig
HH
,
Baltuch
GH
,
Heuer
GG
.
Pediatric indications for deep brain stimulation
.
Childs Nerv Syst
.
2012
;
28
:
1701
14
.
105.
Kaminska
M
,
Lumsden
DE
,
Ashkan
K
,
Malik
I
,
Selway
R
,
Lin
JP
.
Rechargeable deep brain stimulators in the management of paediatric dystonia: well tolerated with a low complication rate
.
Stereotact Funct Neurosurg
.
2012
;
90
:
233
9
.
106.
Tagliati
M
,
Krack
P
,
Volkmann
J
,
Aziz
T
,
Krauss
JK
,
Kupsch
A
, et al
.
Long-Term management of DBS in dystonia: response to stimulation, adverse events, battery changes, and special considerations
.
Mov Disord
.
2011
;
26
:
S54
62
.
107.
Koy
A
,
Bockhorn
N
,
Kühn
AA
,
Schneider
GH
,
Krause
P
,
Lauritsch
K
, et al
.
Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia
.
Brain Stimul
.
2019
;
12
:
1111
20
.
108.
Cheung
T
,
Zhang
C
,
Rudolph
J
,
Alterman
RL
,
Tagliati
M
.
Sustained relief of generalized dystonia despite prolonged interruption of deep brain stimulation
.
Mov Disord
.
2013
;
28
:
1431
4
.
109.
Ruge
D
,
Cif
L
,
Limousin
P
,
Gonzalez
V
,
Vasques
X
,
Coubes
P
, et al
.
Longterm deep brain stimulation withdrawal: clinical stability despite electrophysiological instability
.
J Neurol Sci
.
2014
;
342
:
197
9
.
110.
Wolf
ME
,
Blahak
C
,
Schrader
C
,
Krauss
JK
.
Longterm improvement after cessation of chronic deep brain stimulation in acquired dystonia
.
Tremor Other Hyperkinet Mov
.
2021
;
11
:
29
.
111.
Vidailhet
M
,
Vercueil
L
,
Houeto
JL
,
Krystkowiak
P
,
Lagrange
C
,
Yelnik
J
, et al
.
Bilateral, pallidal, deep-brain stimulation in primary generalised dystonia: a Prospective 3 Year Follow-up Study
.
Lancet Neurol
.
2007
;
6
:
223
9
.
112.
Tisch
S
,
Zrinzo
L
,
Limousin
P
,
Bhatia
KP
,
Quinn
N
,
Ashkan
K
, et al
.
Effect of electrode contact location on clinical efficacy of pallidal deep brain stimulation in primary generalised dystonia
.
J Neurol Neurosurg Psychiatry
.
2007
;
78
:
1314
9
.
113.
Berman
BD
,
Starr
PA
,
Marks
WJ
,
Ostrem
JL
.
Induction of Bradykinesia with Pallidal deep brain stimulation in patients with cranial-cervical dystonia
.
Stereotact Funct Neurosurg
.
2009
;
87
(
1
):
37
44
.
114.
Garcia Ruiz
PJ
,
Ayerbe
J
,
Bader
B
,
Danek
A
,
Sainz
MJ
,
Cabo
I
, et al
.
Deep brain stimulation in chorea acanthocytosis
.
Mov Disord
.
2009
;
24
:
1546
7
.
115.
Mehrkens
JH
,
Bötzel
K
,
Steude
U
,
Zeitler
K
,
Schnitzler
A
,
Sturm
V
, et al
.
Long-term efficacy and safety of chronic globus pallidus internus stimulation in different types of primary dystonia
.
Stereotact Funct Neurosurg
.
2009
;
87
:
8
17
.
116.
Vasques
X
,
Cif
L
,
Gonzalez
V
,
Nicholson
C
,
Coubes
P
.
Factors predicting improvement in primary generalized dystonia treated by pallidal deep brain stimulation
.
Mov Disord
.
2009
;
24
:
846
53
.
117.
Ruge
D
,
Cif
L
,
Limousin
P
,
Gonzalez
V
,
Vasques
X
,
Hariz
MI
, et al
.
Shaping reversibility? Long-term deep brain stimulation in dystonia: the relationship between effects on electrophysiology and clinical symptoms
.
Brain
.
2011
;
134
:
2106
15
.
118.
Ben-Haim
S
,
Flatow
V
,
Cheung
T
,
Cho
C
,
Tagliati
M
,
Alterman
RL
.
Deep brain stimulation for status dystonicus: a case series and review of the literature
.
Stereotact Funct Neurosurg
.
2016
;
94
:
207
15
.
119.
Cao
Z
,
Yao
H
,
Bao
X
,
Wen
Y
,
Liu
B
,
Wang
S
, et al
.
DYT28 responsive to pallidal deep brain stimulation
.
Mov Disord Clin Pract
.
2019
;
7
:
97
9
.
120.
Dafsari
HS
,
Sprute
R
,
Wunderlich
G
,
Daimagüler
HS
,
Karaca
E
,
Contreras
A
, et al
.
Novel mutations in KMT2B offer pathophysiological insights into childhood-onset progressive dystonia
.
J Hum Genet
.
2019
;
64
:
803
13
.
121.
Canaz
H
,
Karalok
I
,
Topcular
B
,
Agaoglu
M
,
Yapici
Z
,
Aydin
S
.
DBS in pediatric patients: institutional experience
.
Childs Nerv Syst
.
2018
;
34
:
1771
6
.
122.
Owen
T
,
Adegboye
D
,
Gimeno
H
,
Selway
R
,
Lin
JP
.
Stable cognitive functioning with improved perceptual reasoning in children with dyskinetic cerebral palsy and other secondary dystonias after deep brain stimulation
.
Eur J Paediatr Neurol
.
2017
;
21
:
193
201
.
123.
Levi
V
,
Zorzi
G
,
Messina
G
,
Romito
L
,
Tramacere
I
,
Dones
I
, et al
.
Deep brain stimulation versus pallidotomy for status dystonicus: a single-center case series
.
J Neurosurg
.
2019
;
134
:
197
207
.
124.
Liu
Z
,
Liu
Y
,
Yang
Y
,
Wang
L
,
Dou
W
,
Guo
J
, et al
.
Subthalamic nuclei stimulation in patients with pantothenate kinase-associated neurodegeneration (PKAN)
.
Neuromodulation
.
2017
;
20
:
484
91
.
125.
Vercueil
L
,
Pollak
P
,
Fraix
V
,
Caputo
E
,
Moro
E
,
Benazzouz
A
, et al
.
Deep brain stimulation in the treatment of severe dystonia
.
J Neurol
.
2001
;
248
:
695
700
.
126.
Benato
A
,
Carecchio
M
,
Burlina
A
,
Paoloni
F
,
Sartori
S
,
Nosadini
M
, et al
.
Long-term effect of subthalamic and pallidal deep brain stimulation for status dystonicus in children with methylmalonic acidemia and GNAO1 mutation
.
J Neural Transm
.
2019
;
126
:
739
57
.
127.
Skogseid
IM
,
Røsby
O
,
Konglund
A
,
Connelly
JP
,
Nedregaard
B
,
Jablonski
GE
, et al
.
Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation
.
J Neurodev Disord
.
2018
;
10
:
17
.
128.
Elkay
M
,
Silver
K
,
Penn
RD
,
Dalvi
A
.
Dystonic storm due to Batten’s disease treated with pallidotomy and deep brain stimulation
.
Mov Disord
.
2009
;
24
:
1048
53
.
129.
Romito
LM
,
Zorzi
G
,
Marras
CE
,
Franzini
A
,
Nardocci
N
,
Albanese
A
.
Pallidal stimulation for acquired dystonia due to cerebral palsy: beyond 5 years
.
Eur J Neurol
.
2015
;
22
:
426
e32
.
130.
Gill
S
,
Curran
A
,
Tripp
J
,
Melarickas
L
,
Hurran
C
,
Stanley
O
.
Hyperkinetic movement disorder in an 11-year-old child treated with bilateral pallidal stimulators
.
Dev Med Child Neurol
.
2001
;
43
:
350
.
131.
Franzini
A
,
Cordella
R
,
Rizzi
M
,
Marras
CE
,
Messina
G
,
Zorzi
G
, et al
.
Deep brain stimulation in critical care conditions
.
J Neural Transm
.
2014
;
121
:
391
8
.
132.
Krause
M
,
Fogel
W
,
Tronnier
V
,
Pohle
S
,
Hörtnagel
K
,
Thyen
U
, et al
.
Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration
.
Mov Disord
.
2006
;
21
(
12
):
2255
7
.