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Deep Brain Stimulation for Pediatric Dystonia

Travis Larsh MD , Steve W. Wu MD , Sudhakar Vadivelu DO ,

Gerald A. Grant MD , Jennifer A. O’Malley MD, PhD

PII: S1071-9091(21)00024-3
DOI: https://doi.org/10.1016/j.spen.2021.100896
Reference: YSPEN 100896

To appear in: Seminars in Pediatric Neurology

Please cite this article as: Travis Larsh MD , Steve W. Wu MD , Sudhakar Vadivelu DO ,
Gerald A. Grant MD , Jennifer A. O’Malley MD, PhD , Deep Brain Stimulation for Pediatric Dys-
tonia, Seminars in Pediatric Neurology (2021), doi: https://doi.org/10.1016/j.spen.2021.100896

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Title: Deep Brain Stimulation for Pediatric Dystonia

Authors: Travis Larsh, MDa; Steve W. Wu, MDb,c; Sudhakar Vadivelu, DOd; Gerald A.
Grant, MDe; and Jennifer A. O’Malley, MD, PhDf*
a
Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH,

USA

b
Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH,

USA

c
Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA

d
Division of Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati,

OH, USA

e
Department of Neurosurgery, Division of Pediatric Neurosurgery, Stanford University

School of Medicine, Palo Alto, CA, USA

f
Department of Neurology, Division of Child Neurology, Stanford University School of

Medicine, Palo Alto, CA, USA

*
Corresponding Author: Jennifer A. O’Malley MD/PhD omalleyj@stanford.edu

Declarations of Interest: None

Abstract:

Dystonia is one of the most common pediatric movement disorders and can have a pro-

found impact on the lives of children and their caregivers. Response to pharmacologic

treatment is often unsatisfactory. Deep brain stimulation (DBS) has emerged as a prom-

ising treatment option for children with medically refractory dystonia. In this review we

highlight the relevant literature related to DBS for pediatric dystonia, with emphasis on

the background, indications, prognostic factors, challenges, and future directions of pe-

diatric DBS.

Keywords: Cerebral palsy, inherited dystonia, acquired dystonia, globus pallidus,

movement disorder, DBS, pediatric dystonia, deep brain stimulation

Introduction:

Background

Dystonia is defined as “a movement disorder characterized by sustained or intermittent

muscle contractions causing abnormal, often repetitive, movements, postures, or both” 1.

Dystonia is currently classified according to its clinical characteristics (age at onset,

body distribution, temporal pattern, and associated features) and etiology (nervous sys-

tem pathology, inherited, acquired, or idiopathic) 1. Underlying dysfunction of complex

neural networks incorporating signaling from a number of brain regions, including the

motor and sensory cortices, basal ganglia, cerebellum, brainstem, and spinal cord con-

tribute to dystonia2–5. Pediatric dystonia can be due to underlying genetic or acquired

etiologies. It can be isolated or combined with other movement or neurologic abnormali-

ties. Pharmacologic treatment of dystonia is limited both by efficacy and side effects,

often with limited or suboptimal clinical effect and sometimes with detrimental long term

effects6, 7.

Deep brain stimulation (DBS) is a now well established treatment for a number of

movement disorders in both adults and children8–11. DBS was first introduced in 1987

and thereafter gained United States’ Food and Drug Administrator (FDA) approval for

tremor (1997) and Parkinson’s disease (2001)12, 13. In 1996, an 8 year old girl with se-

vere generalized dystonia became the first child to receive DBS 14. The globus pallidus

pars interna (GPi) was targeted bilaterally, with reported efficacy 20 years later from the

procedure15. The FDA granted a humanitarian device exemption for pharmacologic re-
sistant dystonia in children age 7 years and older in 2003. Since then, use of DBS in

carefully selected younger children has also demonstrated benefit16–19.

Targets and mechanism

Despite the long term established success of DBS in a variety of conditions, the exact

mechanisms of DBS are still not completely understood. There are likely numerous

overlapping mechanisms that contribute to DBS modulation of pathologic activity20–26.

Intraoperative recordings have contributed to insights in the pathophysiology underlying

dystonia. In dystonia, pathological low frequency (4-12 Hz) pallidal activity has been de-

scribed in local field potential (LFP) recordings and there is evidence that DBS sup-

presses this pathologic activity26. Over 20 years after the first pediatric DBS case, the

GPi remains the most commonly targeted site for pediatric dystonia and GPi stimulation

has been shown to be efficacious in both short term and long term follow-up8, 11, 27. The

subthalamic nucleus (STN) has also proven to be an efficacious target28, 29. Target se-

lection can be particularly challenging in children with dystonia secondary to underlying

brain injury given wide heterogeneity of injury distribution, individualized anatomic ef-

fects, and abundant remodeling of neuronal circuitry that can occur not only immediately

post-injury but also throughout development. Recently, to address the complex issue of

ideal target selection for DBS for children with dystonia, Sanger and colleagues intro-

duced a new targeting protocol in which temporary depth electrodes are placed at mul-

tiple possible targets in the basal ganglia and thalamus and are subsequently probed for

efficacy during a one week inpatient admission19, 30. This approach significantly influ-
enced surgical target choice and led to final electrode placement in locations that would

not have otherwise been selected. This pre-implantation stimulation protocol may repre-
19, 30
sent a promising approach in target selection for acquired dystonia in children .

Patient Selection

Patient selection criteria for pediatric DBS continue to evolve31–34. Generally accepted

inclusion criteria require establishing an unequivocal diagnosis of dystonia, medical

treatment failure, and sufficient disability to the patient or caregivers to warrant sur-

gery34. Relative exclusion criteria include: very young age (generally less than 7 years

old, although younger children may be considered on a case by case basis depending

on severity, etiology, and medical intractability), low weight, high infection risk, inability

to adequately follow-up, active suicidal ideation, and unrealistic expectations34. The eti-

ology of dystonia is considered, particularly what surgical outcome can be expected

based on the available evidence for a given etiology. A discussion of specific conditions

is provided later in this review. For now, we will discuss general outcomes and predic-

tive factors. In patients with a suspected genetic etiology, genetic testing can help in-

form discussions as identification of specific gene mutations can predict likelihood of

beneficial response to DBS35. Pallidal DBS appears to be most effective in patients with

isolated dystonia, irrespective of underlying etiology33. In general, patients with primary

dystonia tend to demonstrate greater and more consistent improvements than those

with acquired dystonia16, 36, 37. Younger patients with shorter disease duration tend to

have greater and more lasting benefit from DBS compared to older patients with more
prolonged dystonia16, 36–40. The proportion of life lived with dystonia inversely correlates

with response to GPi DBS in both primary and secondary dystonia 16. This suggests that

earlier interventions may improve DBS outcomes, reduce childhood experience of dys-

tonia, and reduce the possibility of fixed musculoskeletal deformities as a result of dys-

tonia16. Poorer outcomes are seen in patients with secondary dystonia without a period

of normal development16. A recent meta-analysis of DBS in pediatric dystonia reported

that predictors of better outcomes included: older age at dystonia onset, idiopathic or

inherited dystonia without nervous system pathology, and truncal involvement 41. Other

factors that correlate with improvement from DBS include lower baseline severity, DYT-

TOR1A status, and lack of fixed skeletal deformity37, 39, 40, 42, 43. Therefore, referral to a

DBS center should be considered earlier in the disease course of medically refractory

dystonia, rather than as a “last ditch effort” in long standing disease with accumulated

joint contractures. Ideally, each patient considered for DBS should be evaluated with a

comprehensive interdisciplinary approach that includes the following expertise: pediatric

neurology, pediatric movement disorders specialist with experience in the use of DBS, a

neurosurgery team with expertise in stereotactic technique and DBS implantation in

adults and children, an identified adult DBS specialist to address future needs when pa-

tient is ready for transition to adult care, pediatric and adolescent psychiatry, skilled

nursing staff, neuropsychology, pediatric physical, occupational, and speech therapists

with experience in treatment of pediatric dystonia. Further, we recommend each pediat-

ric DBS case undergoes pre-surgical evaluation by an institution DBS review board,

akin to a tumor board or epilepsy surgery board, consisting of pediatric and adult neu-
rologists, neurosurgeons, physical and occupational therapists, and any other providers

involved in the pre- and post-surgical care for the child.

DBS implantation

In contrast to adults, where patients are awake for a portion of the procedure, DBS

placement in children is usually performed under general anesthesia, owing to in-

traoperative safety concerns (especially in children with marked hyperkinesis). In the

“earlier” days of pediatric DBS, select groups used awake protocols using microelec-

trode recording (MER) to guide electrode placement that incorporated modest sedation,
13
anxiolytic agents, local anesthetic, and child life specialists . However, interventional

magnetic resonance imaging (MRI) guided DBS placement provides real time confirma-

tion of DBS placement and has demonstrated accuracy and clinical outcomes that are

comparable to traditional placement techniques and has universally supplanted awake

MER guided placement in children44, 45. DBS surgery is typically completed via a 2-

stage approach. In Stage 1; the intracranial DBS electrodes are implanted into the pre-

determined brain target tissue typically using the above mentioned MRI-guided stereo-

tactic approach. Leads tips extending from the deeply implanted electrodes are protect-

ed with a surgical “boot” at the skull in preparation for Stage 2. In Stage 2, typically 1-4

weeks after Stage 1, a second surgery is performed to place the implantable pulse gen-

erator (IPG). The IPG combines a small supercomputer and battery, similar in size and

shape to a cardiac pacemaker, and may even be described to a patient as a “brain

pacemaker.” The IPG is typically implanted in the chest beneath the skin (or sometimes
underneath the pectoral muscle for cosmetic reasons), and is positioned much like a

cardiac pacemaker. Lead tips from Stage 1 are connected to an extension piece and

subsequently anchored to the skull. The extension is then placed through a catheter

that has been tunneled behind the ear, down the neck and over the clavicle to reach the

IPG in the chest, thus completing connection between the IPG and the intracranial elec-

trodes. Later, typically about 1 month after Stage 2, the programming clinician can then

use a handheld device to communicate with the patient’s IPG to design and drive pro-

grammed therapeutic stimulation from the intracranial electrode. Although a one-stage

approach may seem appealing in children for obvious reasons, this has been associat-

ed with unacceptably high infection rates when compared to the now “gold standard”

two stage approach 13, 45.

Discussion:

Primary Dystonias

DYT-TOR1A

DYT-TOR1A (DYT1) is the most common hereditary dystonia and is the result of

a heterozygous mutation in the TOR1A gene. Symptom onset is typically during

childhood, beginning as a focal dystonia in an extremity (typically lower extremi-

ty) and generalizing by the early teenage years46, 47. Pharmacologic therapies

have variable and often unsatisfactory results. DYT-TOR1A dystonia has

emerged as a clear indication for DBS.

Children with primary dystonia, including DYT-TOR1A, demonstrate greater im-

provements in Burke-Fahn-Marsden Dystonia Rating Scale motor score

(BFMDRS-MS) than children with other etiologies, and these improvements

negatively correlate with disease duration and the ratio of disease duration nor-

malized to age at the time of surgery16, 40. GPi DBS has consistently found to be

markedly beneficial in DYT-TOR1A, with reported improvements ranging from

42.9-100% (with a majority reporting >60% improvement) at follow-up ranging

from 3 months to 15 years17, 37, 48–55. Due to improvements with DBS, one center

reported 61% of patients had discontinued all dystonia related medications at last

follow-up and 91% had discontinued at least one55. There is growing evidence

that the STN may be efficacious as well, with long term reported improvements

ranging from 70.4-90.4% in BFMDRS-MS29, 56. It is important to recognize that

clinical improvements tend to increase with time with DBS in DYT-TOR1A 50, 51.

DYT-THAP1

DYT-THAP1 (DYT6), caused by an autosomal dominantly inherited THAP1 gene

mutation, also may present as isolated dystonia, but tends to have more promi-

nent cranial involvement compared to DYT-TOR1A46. Motor symptoms of pa-

tients with DYT-THAP1 also tend to respond DBS, with the caveat that DBS has

a marginal impact on dysphonia57. However, several authors have reported im-

provement in speech and swallowing following GPi DBS58–60. Patients with DYT-

THAP1 seem to have a clinically significant, but more modest, response to DBS
compared to DYT-TOR1A 61. However, others have reported that in comparison

to DYT-TOR1A, patients with DYT-THAP1 improved less dramatically in early fol-

low-up but similarly in long term follow-up62. Reported improvements (with follow-

up ranging from 1-7.7 years) in BFMDRS-MS range from 42.2-58% 41, 61, 63, 64.

Some have reported greater benefit in younger patients with less disease dura-

tion, while others have not found age or disease duration to be significant predic-

tive factors in DYT-THAP163, 64. The GPi was the target almost universally in re-

ports of DYT-THAP1 patients undergoing DBS; one adult patient with longstand-

ing limb dystonia and spasmodic dysphonia with initial poor response to pallidal

DBS underwent bilateral ventral lateral anterior (VLa) thalamic nucleus DBS with

improvement in BFMDRS total score by more than 80% at 2 year follow-up65.

DYT-SGCE

DYT-SGCE (DYT11, myoclonus-dystonia syndrome, MDS), caused by pathogen-

ic mutations in the SGCE gene, is characterized by childhood onset myoclonus

and dystonia, preferentially involving the upper body, and can frequently be re-

fractory to medical treatment. Unfortunately, this diagnosis is often missed during

childhood and reports of children undergoing DBS are rare66. Patients with MDS

with and without SGCE mutations were among patients classified as “primary

dystonia” in a meta-analysis demonstrating patients with this categorization have

greater improvements in BFMDRS-MS than those of other etiologic categories;

patients that were younger and with less dystonia duration had more improve-

ment16.

The ventral intermediate nucleus of the thalamus (VIM) and GPi have been re-

ported as targets for DBS in DYT-SGCE. DBS of either the VIM or GPi seems to

be beneficial for both myoclonus and dystonia, but GPi DBS appears to have

greater efficacy for dystonia67. Improvements in both myoclonus (Unified Myoclo-

nus Rating Scale, UMRS) and dystonia (BFMDRS-MS) are consistently reported

as greater than 50% after DBS in DYT-SGCE37, 41, 66–71. In addition to finding

marked improvements in motor disability, more recently, improvement in quality

of life and social adaptation has been noted in DYT-SGCE patients after GPi

DBS72, 73.

Wang et al reported 2 patients with mutations in both TOR1A and SGCE that un-

derwent DBS and improved by 80.2% in BFMDRS-MS and 98.6% in UMRS74.

DYT-KCTD17

DYT-KCTD17 (DYT26), a result of heterozygous mutations in the KCTD17 gene,

is a more recently described cause of MDS, with reported clear benefit in a 17

year old patient that underwent GPi DBS75–77. DYT-KCTD17 may be responsible

for some previously reported SGCE negative cases of MDS75, 76.

DYT-ATP1A3

DYT-ATP1A3 (DYT12) is due to a heterozygous pathogenic mutation in the

ATP1A3 gene and is characterized by rapid onset dystonia-parkinsonism that is

typically refractory to pharmacologic management. Recently, a pair of monozy-

gotic twins with dystonia and paroxysmal attacks, resembling paroxysmal non-

kinesigenic dyskinesias, due to a novel ATP1A3 mutation were reported with im-

provement in interictal dystonia and resolution of paroxysmal attacks with oral

levodopa and bilateral GPi DBS78. Unfortunately, DBS appears to be of minimal

benefit in other reported cases of DYT-ATP1A379–83.

DYT-KMT2B

DYT-KMT2B (DYT28) is characterized by childhood onset, progressive, general-

ized dystonia with accompanying choreoathetosis, myoclonus, intellectual disa-

bility, and developmental delays. Cif et al recently published on the long term ef-

ficacy of DBS in DYT-KMTB84. Eighteen patients were included, median age of

implantation was 11.5 years, and follow-up ranged from 3 months to 22 years,

including 8 patients with at more than 5 years of follow-up84. At 1 year post-DBS,

more than 50% of patients experienced greater than 30% improvements in

BFMDRS-MS and disability scores (BFMDRS-DS); this was respectively main-

tained in 5/8 and 3/8 patients after 5 years84. The greatest benefit was in trunk

and cervical dystonia, DBS significantly improved quality life, except in regards to

laryngeal dysphonia which did not improve significantly with DBS84.

Others have similarly reported sustained and significant benefits after GPi DBS in

KMT2B related dystonia85–89.

GNAO1
 GNAO1 gene mutations are known to cause an epileptic encephalopathy, as well

as a progressive movement disorder that may feature recurrent episodes of se-

vere hyperkinesia with dystonia, choreoathetosis, and ballism. DBS (all reports

thus far are of the GPi) has emerged as a useful and potentially lifesaving proce-

dure in these patients. Several have reported acute improvement and long term

near or complete resolution in severe hyperkinetic episodes following GPi DBS 90–
93
. DBS also appears to improve the severity of interictal dystonia and hyperkine-

sis, with significantly improved quality of life reported among caregivers94–96.

Other Genetic Dystonias

Neurodegeneration with brain iron accumulation disorders

Neurodegeneration with brain iron accumulation (NBIA) disorders are a group of

neurodegenerative diseases characterized by abnormal iron accumulation in the

brain. The most common NBIA disorder in regards to patients with DBS is panto-

thenate kinase associated neurodegeneration (PKAN). The reported short and

long term response of PKAN to DBS is variable16, 17, 37, 97–104. The authors of a re-

cent meta-analysis including 99 patients with PKAN reported mean improvement

in BFMDRS-MS of 45% and 16% at one year in atypical and classic PKAN, re-

spectively105. Seventy-three percent of atypical cases had at least a 30% im-

provement, versus 34% in classic cases105. Higher preoperative BFMDRS-MS

and atypical type predicted better outcomes; GPi DBS improved BFMDRS-DS

significantly in atypical but not classical cases105. There have been reports of

dramatic response to GPi DBS in the setting of opisthotonus and acute dystonic
 crises106, 107. The vast majority of PKAN cases have been GPi implants; the STN

may be an intriguing target given the preference for pallidal iron deposition105, 108.

There is a report of a patient with PLA2G6-associated neurodegeneration

(PLAN) received bilateral VIM and GPi DBS for an acute dystonic crisis, with

good response109. A single patient with mitochondrial membrane protein-

associated neurodegeneration (MPAN) had excellent benefit from GPi DBS110.

Lesch-Nyhan disease

Lesch-Nyhan disease (LND) is an X-linked recessive disorder caused by muta-

tions in the HPRT1 gene. Dystonia generally seems to respond well to GPi DBS

in LND, although results are variable and reports are sparse41, 111. Self-mutilating

behaviors, which cause significant disability to patients and caregivers, has re-

sponds significantly to DBS in some reports112, 113. There is growing evidence

that secondary self-injurious behaviors in conditions other than LND may also be

amenable to DBS114.

Glutaric aciduria type 1

Glutaric aciduria type 1 (GA1) is caused by homozygous pathogenic mutations in

the GCDH gene. There are sparse reports of GA1 patients receiving GPi DBS,

with minimal improvement noted in BFMDRS motor and disability scores17, 41, 115.

Secondary/Structural Causes of Dystonia

Cerebral Palsy
Cerebral palsy (CP) encompasses a broad and heterogeneous patient population

that is the most common etiology of acquired dystonia in childhood. Compared to

primary dystonia, the response of a patient with CP to DBS is difficult to predict,

owing to the heterogeneity of this patient cohort17, 18, 51, 116–118. Carefully selected

patients may have significant and durable response to GPi DBS, with younger

age possibly a positive predictive factor while higher pre-operative dystonia se-

verity and co-occurrence of spasticity are negative predictive factors for DBS re-

sponse51, 117, 119–121. Usually other co-occurring hyperkinetic movement disorders

are not worsened by DBS although the programming clinician should be aware of

dyskinesias or other side effects which may result from overstimulation and ad-

just DBS settings accordingly. Confounding the assessment of DBS in CP (and

other pediatric dystonia) is the insensitivity of traditional dystonia rating scales in

this patient cohort, with significant changes in functional performance, satisfac-

tion, and dystonic pain noted, even in the absence of objective changes in rating

scale scores120, 122–124. Individualized target selection is of particular importance

in this patient population, where ideal target selection is highly dependent on in-

tegrity of existing target tissue for each patient.

Other structural causes of dystonia

Regarding other causes of pediatric secondary dystonia, such as stroke and ker-

nicterus, a highly variable individual response to DBS has been reported in a

very limited number of patients19, 41.

Status dystonicus

Status dystonicus is a life threatening, movement disorder emergency. Regardless of

underlying etiology, amongst reported cases, DBS has resolved over 90% of such cas-

es and is likely underutilized in this life-threatening situation125–127.

Challenges

Complications

Precise complication rates for DBS in pediatric dystonia are unknown. The only

prospective study on complication rate in pediatric dystonia found surgical site in-

fection rates of 10.3% and complications related to electrodes and extensions of

18%, including 12.3% rate of lead fracture128. Recently published data collected

by the German registry on pediatric DBS (GEPESTIM) reported the total risk of

an adverse event requiring surgical intervention was 7.9% per electrode-year, in-

cluding a 12.5% rate of wound infections and 29.2% rate of hardware related is-

sues129. Using a multistage surgical approach and improvements in device de-

sign, such as smaller, rechargeable IPGs may be helpful in reducing the risk of

surgical infection and hardware complications amongst pediatric DBS patients 13,
17, 45, 53, 128, 130, 131
. If clinical response to DBS becomes unsatisfactory in a patient

with previously robust response, evaluation of electrode position (and revi-

sion/reimplantation if necessary) should be considered132, 133.

Imaging after DBS Implantation

Although most DBS systems are now MR-compatible, there are limitations to the

sequences which can be done safely. Generally, T2-weighted sequences should

be avoided in patients with DBS due to increased risk of heating 134. Patients with

DBS have safely received 3-T MRI 134, 135. To ensure optimum patient safety and

imaging quality, DBS vendors should be consulted regarding specific MRI guide-

lines for their respective DBS systems.

Outcome Measures

The BFMDRS and Barry-Albright Dystonia (BAD) scale are the most common

tools used to assess the effect of DBS in children with dystonia. Despite their

widespread use, limitations include lack of validation in children (BFMDRS), large

inter-rater variability, assessment of a single symptom (dystonia), and inability to

discriminate between abnormal postures and non-dystonic movements136. These

scales are particularly deficient in ability to assess meaningful changes in non-

primary dystonia, particularly when impairment is severe. They are unable to

capture the full effect of DBS (or other interventions) on children and their fami-

lies, particularly in regards to function and quality of life.

The limitations associated with these commonly used dystonia scales highlight

the difficulty in accurately describing and measuring improvement post DBS for

children with complex movement disorders. The nature and severity of disability

is multifactorial and unique to each child, stressing the need for individualized

assessment of post-surgical impact across multiple functional domains. Compre-

hensive post-DBS assessment demands inclusion of additional domains such as

enhanced comfort, decreased caregiver burden, improved autonomy and inde-

pendence in self-care, and personalized goal setting. The Movement Disorder-

Childhood Rating Scale (MD-CRS) does included assessment of motor function-

 ing, dysphagia, self-care limitations and attention/alertness issues and is worth

consideration for pre- versus post- DBS clinical improvement and may be a use-

ful tool for quantification of post-DBS improvement in the future. Other scales

such as The Canadian Occupational Performance Measure (COPM) and Goal

Attainment Scaling (GAS), tools commonly used by allied health professionals,

have been effective in assessing patient/family satisfaction and identifying patient

and caregiver-driven functional goals and changes associated with DBS136–138.

To best identify patients who may benefit from DBS, the development of sensi-

tive, disease specific measurements that adequately assess the impact of DBS

on the lives of children and their caregivers is vital.

Referral to pediatric DBS programs

Early referral for evaluation for pediatric DBS is integral in producing the best outcomes

for patients. The number of centers performing pediatric DBS continues to grow. If a re-

ferring provider is unsure of where to refer their patient for evaluation, local pediatric

movement disorder specialists, established adult DBS programs or medical device

companies may be helpful in providing guidance. PEDiDBS is an international pediatric

deep brain stimulation registry of centers performing pediatric DBS

(www.pedidbs.org)139. In addition to DBS, children with cerebral palsy may benefit from

other surgical procedures, such as an intrathecal baclofen pump. There is currently no

standardized process of determining which surgery to recommend.

Programming techniques
There are no evidence based guidelines available to guide pediatric DBS programming

and optimal stimulation parameters vary by surgical target. Partnering with

programming experts is essential in optimizing the clinical outcome of DBS placement in

children. DBS device company representatives are often an outstanding resource as

these individuals gain exposure to a number of clinical practices and a wide variety of

patients. Patience is particularly key when programming DBS in children; clinical benefit

may be slow to reveal. For example, while phasic dystonic movements may be relieved

within minutes of stimulation onset, improvements in tonic posturing manifest over

several months140, 141. Higher voltages are often needed for dystonia compared to other

DBS indications, an important consideration in regards to battery life, with rechargeable

systems being preferable. High frequency (typically 130-160 Hz) stimulation is most

commonly used, but lower frequencies (60 Hz) have been reported as similar in efficacy

and are helpful in prolonging battery life and sometimes minimizing side effects of over-

stimulation142–145. Narrow pulse widths may be similar in efficacy to wider pulse widths

depending on electrode placement and the specific target142, 144, 145. It is important to

remember that overstimulation can be equally problematic to understimulation, and

should be considered if a patient seems to be worsening, developing dyskinetic

movements, or failing to improve despite frequent optimization of stimulation. Possible

overstimulation side effects include phosphenes, dysarthria, dyskinesias, tonic

contractions, mood changes, cognitive slowing, paresthesias, nausea, and malaise.

Finally, given the continued growth and development of children compared to adults,

more frequent programming appointments are often necessary to best accommodate

the unique needs of your pediatric DBS patients.

Conclusions: (Summarized in Table 1)

Properly identifying which patients will benefit from DBS continues to be a key issue

moving forward, particularly in secondary dystonia. To this end, multi-center patient reg-

istries (PEDiDBS and GEPESTIM) have been created to allow data sharing with the

goal of clarifying the role of DBS in pediatric patients. Further elucidating the underlying

mechanisms of DBS and identification of optimum surgical targets is needed, particular-

ly in patients with abnormal neuroanatomy in which alternative targets may provide

more benefit than conventional targets 19, 30, 146–148. In the future, adaptive “closed loop”

DBS systems that respond to underlying neurophysiology are an exciting option that will

hopefully optimize benefit for each individual patient2, 26, 149, 150.

Consider the following when referring and managing a young patient with dysto-
nia for DBS:

1) Optimize medical management: Has the patient tried adequate dosing of mul-
tiple medications including a levodopa trial? Has botulinum toxin been trialed for
focal dystonia?

2) When to refer: Consider DBS for any child with medication-refractory dystonia
regardless of etiology.When is the best time for evaluation for DBS? The earlier
the better; consider a referral for evaluation as soon as dystonia is recognized,
especially when medication refractory.

3) Help set realistic expectations: Post-DBS clinical improvement takes time and
patients may not experience full benefit for months to years after surgery. Be
sure to set realistic expectations with families pre-operatively.

4) Maximize programming: Effective optimization of settings requires frequent

programming sessions with small incremental changes to avoid overstimulation
and unwanted side effects. Programming should be completed by a clinician
with experience in DBS programming in children. DBS device company repre-
sentatives can be essential resources for clinician education and are typically
available to assist with programming visits and other patient equipment needs.

5) Support an evolving care plan: DBS can significantly reduce the need for
 medication and other interventions. Medication dosage and use should be con-
tinuously re-evaluated in concert with ongoing DBS programming and stimula-
tion to ensure patient is on a regimen optimized to his or her evolving needs.

6) Utilize experienced programs: Pediatric DBS candidate are best served by

referral to an institution with an established pediatric DBS program.

Table 1: Take-home points for referral of a young patient with dystonia for DBS and

basic post-implantation management

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Consider the following when referring and managing a young patient with dysto-
nia for DBS:

7) Optimize medical management: Has the patient tried adequate dosing of mul-
tiple medications including a levodopa trial? Has botulinum toxin been trialed for
focal dystonia?

8) When to refer: Consider DBS for any child with medication-refractory dystonia
regardless of etiology.When is the best time for evaluation for DBS? The earlier
the better; consider a referral for evaluation as soon as dystonia is recognized,
especially when medication refractory.

9) Help set realistic expectations: Post-DBS clinical improvement takes time and
patients may not experience full benefit for months to years after surgery. Be
sure to set realistic expectations with families pre-operatively.

10) Maximize programming: Effective optimization of settings requires frequent

programming sessions with small incremental changes to avoid overstimulation
and unwanted side effects. Programming should be completed by a clinician
with experience in DBS programming in children. DBS device company repre-
sentatives can be essential resources for clinician education and are typically
available to assist with programming visits and other patient equipment needs.

11) Support an evolving care plan: DBS can significantly reduce the need for
medication and other interventions. Medication dosage and use should be con-
tinuously re-evaluated in concert with ongoing DBS programming and stimula-
tion to ensure patient is on a regimen optimized to his or her evolving needs.

12) Utilize experienced programs: Pediatric DBS candidate are best served by
referral to an institution with an established pediatric DBS program.

Table 1: Take-home points for referral of a young patient with dystonia for DBS and

basic post-implantation management