Original Article

Journal of Child Neurology

2022, Vol. 37(6) 441-450
Status Dystonicus in Children: A Cross- © The Author(s) 2022
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Sectional Study and Review of Literature DOI: 10.1177/08830738221081593
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Arushi Gahlot Saini, MD, DM1 , Ijas Hassan, MD2,

Kanika Sharma, MD2, Jayashree Muralidharan, MD, DNB3,
Sumeet Dhawan, MD, DM2, Lokesh Saini, MD, DM1 ,
Renu Suthar, MD, DM1 , Jitendra Sahu, MD, DM1,
Naveen Sankhyan, MD, DM1 , and Pratibha Singhi, MD1

Abstract
Background: Status dystonicus is a life-threatening, underrecognized movement disorder emergency. We aimed to ascertain
the etiology, clinical presentation, complications, and outcomes of status dystonicus in children and reviewed the literature
for similar studies. Methods: Records of all children aged <14 years admitted to a single center with status dystonicus between
2014 and 2018 were reviewed. Results: Twenty-four children (75% male) were identified with status dystonicus. The annual
incidence rate was 0.05 per 1000 new admissions <12 years of age. The mean age at presentation was 6.3 ± 3.6 years.
Median duration of hospital stay was 10.5 days (interquartile range 5-21.7). The severity of dystonia at presentation was
grade 3 (n = 9; 37.5%) and 4 (n = 9; 37.5%). The most common triggering factor was intercurrent illness/infection (n = 18;
75%). The most common underlying etiologies were cerebral palsy (n = 8; 33.3%), complicated tubercular meningitis (n = 3;
12.5%), and mitochondrial disorders (n = 3; 12.5%). Basal ganglia involvement was seen in 15 cases (62.5%). Respiratory and/
or bulbar compromise (n = 20; 83.3%) and rhabdomyolysis (n = 15; 62.5%) were most commonly seen. Oral trihexyphenidyl
(96%) followed by oral or intravenous diazepam (71%), oral baclofen (67%), and midazolam infusion (54%) were the most com-
mon drugs used. Clonidine was used in 33% cases, without any significant side effects. Three children died owing to refractory
status dystonicus and its complications; the mortality rate was 12.5%. Conclusion Status dystonicus is a neurologic emergency in
children with severe dystonia, with significant complications and a high mortality rate. Static and acquired disorders are more
common than heredo-familial causes. Identification and treatment of infection in children is important as the majority of
cases are triggered by an intercurrent infection.

Keywords
dystonia, dystonic storm, status dystonicus, dystonic crisis, midazolam

Date received: 13 September 2022; revised: 9 January 2022; accepted: 22 January 2022.

Introduction generalized or focal hyperkinetic movements that have necessi-

The Taskforce on Childhood Movement Disorders has defined
dystonia in the context of hypertonia as a movement disorder in
which involuntarily sustained or intermittent muscle contrac-
tions cause twisting and repetitive movements, abnormal pos-
tures, or both.1 First recognized by Jankovic and Penn in
1982,2 status dystonicus, dystonic storm,3 or dystonic crisis is
a life-threatening movement disorder. It is defined as increas-
ingly frequent or continuous, severe episodes of generalized
dystonia requiring urgent hospital admission.4 In practice, it
often occurs at the end of a continuum of worsening dystonia
in children, unlike convulsive status epilepticus where the
event is “binary” (seizing or not).5 A modified definition for
status dystonicus has been recently proposed as “a movement
disorder emergency characterized by severe episodes of
tated urgent hospital admission because of the direct life-
1
Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of
medical Education and Research (PGIMER), Chandigarh, India
2
Department of Pediatrics, Postgraduate Institute of Medical Education and
Research (PGIMER), Chandigarh, India
3
Pediatric Emergency and Intensive Care Units, Department of Pediatrics,
Postgraduate Institute of Medical Education and Research (PGIMER),
Chandigarh, India
Corresponding Author:
Pratibha Singhi, MD, Pediatric Neurology and Neurodevelopment, Medanta,
The Medicity, CH Baktawar Singh Rd, Sector 38, Gurgaon, 122001, Haryana,
India.
Email: doctorpratibhasinghi@gmail.com
442 Journal of Child Neurology 37(6)

threatening complication(s) of these movements, regardless of ventilatory support (supplemental oxygen or pressure support);
the patient’s neurological condition at baseline.”5,6 (2) rhabdomyolysis as evidenced by myoglobinemia or myoglobi-
Although considered rare, the entity is underreported in chil- nuria or positive urine dipstick for blood, red blood cells on urine
dren because of the lack of an operational definition, variable microscopy, elevated creatine phosphokinase (muscle), elevated
underlying etiology, complex mechanism, management strate- lactate dehydrogenase, increased potassium, increased phosphate,
gies, and outcomes. Specifically, because dystonia is a fluctuat- decreased calcium, increased uric acid, and hypoglycemia with
ing state, its intensity may vary over minutes to days. pancreatic dysfunction; (3) elevated body temperature; (4) electro-
Worsening dystonia in a child may rapidly progress to status lyte abnormalities; (5) exhaustion from sleep deprivation and exer-
dystonicus with complications but it is difficult to ascertain clin- tion; (6) dehydration requiring correction; (7) acute kidney injury;
ically at which point this transition occurs. Hence, in the
absence of clear biomarkers or a quantifiable definition, status
dystonicus often remains underdiagnosed. Children constitute Table 1. Clinical Features of Children With status Dystonicus
up to 60% of the reported cases, but the true incidence is not (n = 24).
known.7 The mean prevalence of status dystonicus among all
Variable n (%)
dystonia patients seen in a multicenter study was 2.8% (range
0.1%-5.6%).8 Hospital-based annual incidence in children has Presenting complaints
been estimated at 0.4/1000 fresh admissions, with an event Abnormal body postures 20 (83.3)
rate of 0.9/1000 admissions.8 The at-risk population includes Fever 9 (37.5)
patients with primary or secondary chronic dystonia, cerebral Walking difficulty and frequent falls 6 (25)
Altered sensorium 5 (20.8)
palsy, neurodegenerative and neurometabolic disorders, espe-
Change in speech 3 (12.5)
cially the ones with involvement of basal ganglia, central Development delay 2 (8.3)
nervous system insults due to infections, vascular events, Vomiting 2 (8.3)
hypoxia, or trauma, and acute drug withdrawal such as baclo- Hemiparesis 1 (4.2)
fen.9 Because of the scarcity of pediatric series on the subject, Cognitive decline 1 (4.2)
we aimed to ascertain the etiology, clinical presentation, and Drooling of saliva 1 (4.2)
outcomes of status dystonicus in children and also reviewed Tremor 1 (4.2)
Severity of dystonia at presentation
the literature for similar studies.
Grade III 9 (37.5)
Grade IV 9 (37.5)
Methodology Grade V 6 (25)
Triggering factors
This retrospective study was conducted in a tertiary care hospi- Intercurrent illness/infection 18 (75)
tal for children between 2014 and 2018. Records of consecutive Not known 3 (12.5)
children up to 12 years of age admitted to the Pediatric Progression of underlying disease 2 (8.3)
Drug-induced or withdrawal 1 (4.2)
Neurology unit with the diagnosis of status dystonicus were
Underlying etiology
retrieved. For the study, patients were defined as having Static insults 15/24 (62.5)
status dystonicus when they developed increasingly frequent Cerebral palsy 8 (33.3)
and severe episodes of generalized dystonia that had necessi- Tubercular meningitis with complications 3 (12.5)
tated urgent hospital admission.4 The demographic details, clin- Hypoxic injury to the brain 2 (8.3)
ical presentation and course, underlying neurologic disease, Autoimmune encephalitis 1 (4.2)
triggering event, complications, and management were noted Cortical venous thrombosis 1 (4.2)
Progressive/heredo-familial 9/24 (37.5)
in a prestructured proforma. The underlying neurologic disorder
Mitochondrial 3 (12.5)
was classified as (1) drug-induced; (2) primary, where dystonia Neuro-Wilson 2 (8.3)
was the sole clinical sign prior to status dystonicus; (3) secondary Pantothenate kinase–associated 2 (8.3)
to a static or progressive neurologic disorder; and (4) dystonia plus neurodegeneration
syndrome (where dystonia was present with other neurologic fea- Suspected organic acidemia 1 (4.2)
tures). The severity of dystonic crisis was assessed using the Primary progressive dystonia 1 (4.2)
5-point Dystonia Severity Action Plan as follows: grade I, sitting
Neuroimaging features (n = 21)
comfortably, regular sleep, stable on medication; grade II, irritable
Normal 2 (9.5)
and cannot settle, dystonic posturing interferes with seating activ- Globus pallidum 11 (52)
ities; grade III, cannot tolerate lying, sleep is disturbed, without Thalamic 5 (24)
signs of metabolic disturbance; grade IV, early multiorgan Putamen 6 (29)
failure; and grade V, immediate life-threatening.10 Medical com- Midbrain 4 (19)
plications were classified broadly into (1) respiratory or bulbar Caudate 4 (19)
compromise (evidenced by frequent desaturations), stridor, Subthalamus 3 (14)
Hydrocephalous 3 (14)
increased feeding support, recent aspiration pneumonia, abnormal
White matter 1 (4.7)
arterial gas analysis, respiratory insufficiency or failure, and
Saini et al 443

(8) hypertension; (9) cardiac or circulatory dysfunction (hypoten- Table 2. Complications Noted in Children With Status Dystonicus
sion, abnormal heart rate or rhythm); and (10) death. Data were During the Hospital Course.
analyzed using SPSS (version 23.0). Descriptive statistics such Complications
as frequency and percentages were calculated for all categorical
variables. Respiratory and/or bulbar compromise 20 (83.3)
Frequent desaturations 3 (12.5)
Stridor 1 (4.1)
Search Strategy Feeding support by nasogastric tube 4 (16.7)
Recent aspiration pneumonia 1 (4.2)
Citations were identified through PubMed using the search Respiratory insufficiency/failure 2 (8.3)
strategy ((((((dystonic storm) OR (status dystonicus)) OR (dys- Supplemental oxygen or ventilatory support 9 (37.5)
tonic crisis)) OR (("desperate"[All Fields] OR "desperately"[All Rhabdomyolysis 15 (62.5)
Fields] OR "desperation"[All Fields]) AND ("dystonic"[All Myoglobinemia (rarely measured) 2 (8.3)
Fields] OR "dystonics"[All Fields]))) OR (life-threatening dys- Elevated creatine phosphokinase (muscle) 6 (25)
tonia)) OR (dystonic state)) AND (((((children) OR (pediatric)) Elevated lactate dehydrogenase 4 (16.7)
Elevated potassium 3 (12.5)
OR (paediatric)) OR (child)) OR (infant)). The search yielded Elevated body temperature 4 (16.7)
367 results on June 15, 2021. Twenty articles were identified Exhaustion from sleep deprivation and exertion 2 (8.3)
where atleast ≥3 patients or >3 dystonic episodes were Dehydration requiring correction 5 (21)
studied. These were manually searched for patients fulfilling Electrolyte disturbance 3 (12.5)
the inclusion criteria (status dystonicus). We also reviewed Acute renal failure 2 (8.3)
the cross-references of the relevant articles, and the final refer- Bulbar dysfunction 2 (8.3)
ence list was based on the relevance to the topic of review. Only Cardiac/circulatory dysfunction 3 (12.5)
Death 3 (12.5)
articles published in English were reviewed. Fourteen previ-
ously published series were identified.
96%), oral or intravenous diazepam (n = 17; 71%), oral baclo-
Results fen (n = 16; 67%), and intravenous midazolam infusion or
During the study period, 83 076 children were hospitalized in oral clonazepam/clobazam (n = 13; 54% each). Oral melatonin
the Department of Pediatrics. Of these, 45 children were (38%) and oral or intravenous clonidine (33%) were used, and
labeled as having status dystonicus in their medical records. there were no significant side effects warranting discontinuation
Of these, 21 cases had intermittent dystonia without any pro- of these drugs. The details of medications used to control status
gression or complication and responded to oral medications; dystonicus are shown in Figure 2. Together with the present
hence were excluded. Status dystonicus was noted in 24 cases series, the summary of the studies selected as per the search
and were further analyzed. This led to an annual incidence strategy is presented in Table 3.
rate of 0.05 per 1000 new admissions below 12 years of age.
The majority were male (n = 18; 75%), and the mean age of pre-
sentation was 6.3 ± 3.6 years (range 7 months to 12 years). The
Discussion
age distribution was as follows: <5 years (n = 9; 37.5%), Our study is the largest pediatric study on status dystonicus
between 5 and 10 years (n = 12; 50%), and >10 years (n = 3; from a single center and contributes to the sparse literature on
12.5%). All children had generalized dystonia (n = 24; the subject. The study highlights that status dystonicus in chil-
100%). Neuroimaging details were available for 21 children. dren has variable etiology and that most cases are secondary to
The majority of these images were taken prior to admission an underlying static or progressive insult to the brain. Status
for status dystonicus and do not reflect the acute changes of dystonicus is a neurologic emergency with a high mortality
status dystonicus. Of these, abnormal magnetic resonance (12.5%). The annual incidence rate was 0.05 per 1000 new
imaging (MRI) of the brain was noted in the majority of admissions below 12 years of age in our study. The course is
cases (n = 19/21; 90.4%). Basal ganglia involvement was complicated by several systemic complications. We also
found in 15 cases (71.4%). The baseline clinical features and reviewed the literature based on our search strategy and summa-
complications during the course of hospital stay are presented rized the clinical series on pediatric status dystonicus in
in Tables 1 and 2. The underlying causes are presented in Table 3.2,4,7,8,11-20
Figure 1. The median duration of hospital stay was 10.5 days All children in the current study had generalized, severe dys-
(interquartile range 5-21.7). tonia in severity grades III and IV, followed by V. According to
The patients were managed according to the standard man- the Dystonia Severity Action Plan, only grade IV and V would
agement protocol including airway support, hydration, correspond to status dystonicus. However, unlike status epilep-
oxygen and/or ventilation, renal replacement therapy, analge- ticus, status dystonicus is a clinical continuum and it is difficult
sia, sedation, muscle relaxation, nasogastric feeding, antibiotics to ascertain its exact onset in a child with very frequent and dis-
as needed, and antidystonia drugs. The most commonly used turbing dystonia. These children are probably in the “pre–status
drugs for these patients were oral trihexyphenidyl (n = 23; dystonicus” stage (corresponding to stage III) and may rapidly
444 Journal of Child Neurology 37(6)

Figure 1. Underlying causes noted in children with status dystonicus (CP, cerebral palsy; CSVT, cortical sinus venous thrombosis;
PKAN, pantothenate kinase–associated neurodegeneration; TBM, tubercular meningitis).

Figure 2. Antidystonia drugs (%) used in 24 children with status dystonicus.

worsen with metabolic and systemic complications. Hence,
stage III (prior to metabolic and autonomic disturbances) is
probably the best time to initiate aggressive management and
may prevent progression to stage V.6,10 Results from a large,
retrospective multicenter study of 89 episodes of status dystoni-
cus (59% occurring children <15 y) show that the first-line
medical treatment of established status dystonicus was effective
in only 10% of the cases and mortality rate was high (10%).7
Hence, using the Dystonia Severity Action Plan to assess the
severity, grade III dystonia should be included in the spectrum
of status dystonicus and administered emergent care in the
emergency setting.
In our study, static disorders were the underlying cause in
two-thirds of the cases, and cerebral palsy was most common
among these. Cerebral palsy is also the most common cause
of dystonia and status dystonicus in childhood.8,12,21 A
similar preponderance of secondary dystonia and status
dystonicus due to acquired insults was seen in a large multicen-
ter study from Italy and a retrospective study from India.7,8
Overall, status dystonicus has been associated with central
nervous system disorders such as hypoxic ischemic encepha-
lopathy, inflammatory, autoimmune, encephalitis, vascular
(Moyamoya), neurometabolic, and drug-induced movement
disorders.9,22 A clinical differentiation from hyperkinetic move-
ment disorder emergencies in anti-N-methyl-D-aspartate
(NMDA) receptor encephalitis or Sydenham chorea has been
suggested based on the preponderance of “strongly choreic fea-
tures” or oromandibular dystonia in these conditions.8,23
Several nondystonic neurologic disorders have been anecdot-
ally associated with the unusual presentation of status dystoni-
cus in case reports across the literature. However, most of the
causes have an underlying involvement of the basal ganglia
or its connections as seen in our study. Children with kernicte-
rus secondary to neonatal hyperbilirubinemia are particularly
 Table 3. A Review of Literature on Status Dystonicus in Children.

Mean age (y)

at onset of
Author, year, dystonia,
population male: female
origin Type of study No. of patients ratio Underlying cause for SD Trigger Modalities used for treatment Outcome

Jankovic and Retrospective N = 2; 3 Both male Primary dystonia in both None L-Dopamine, tetrabenazine, muscle No improvement
Penn 1982, episodes cases paralysis, thalamotomy
USA2
Manji et al Retrospective N = 12; 5 10.8 y, all Athetoid cerebral palsy (n = Introduction of clonazepam (n n = 2/5 children died, n
1998, UK4 children male 3), = 2/5), Benzhexol, pimozide, = 1/5 no
primary torsion dystonia (n none (n = 3/5) tetrabenazine, baclofen, oral and improvement, n = 2/5
= 2) intrathecal diazepam, midazolam improved
infusion, sodium valproate,
carbamazepine, chlormethiazole,
stereotactic thalamotomy
Teive et al Retrospective, N = 5; 2 children 8.5 y, both Cerebral palsy (n = 2) None Diazepam, chlorpromazine, general No mortality, good to
2005, multicenter male anesthesia with propofol, bilateral excellent
Brazil18 pallidotomy, clonazepam,
biperiden, midazolam,
haloperidol, trihexyphenidyl,
levodopa-carbidopa
Zorzi et al Retrospective N = 12 cases of 10.6 y, all Primary dystonia (n = 2), Infection (n = 1), Trihexyphenidyl, oral, and Good outcome, no
2005, dystonia; 3 male secondary dystonia of none identified (n = 2) intrathecal baclofen, clozapine, recurrence of SD in
Italy20 had SD unknown origin (n = 1) carbamazepine, tetrabenazine, follow-up after
pimozide, haloperidol, bilateral surgery
pallidal stimulation
Mariotti et al Retrospective N = 2 children; 14.5 y, both Static encephalopathy of Infection (100%) Midazolam, deep sedation, propofol, Improved
2007, 6 episodes male undetermined etiology (n thiopental, anesthesia baclofen
Italy14 = 1) and PKAN (n = 1) pump, DBS of globus pallidus
Paliwal et al Retrospective N=3 13.3 y, 2:1 Wilson disease (n = 3) D-Penicillamine induced Gabapentin, trihexyphenidyl, Improved
2010, diazepam, levodopa,
India17 tetrabenazine
Fasano et al Retrospective, N = 68; 89 16.4 y, 1.7:1 Secondary dystonia (37.8%), Infection (51.7%), Tetrabenazine, benzhexol, Death (n = 7; 10.3%),
2012, Italy7 multicenter episodes in heredo-degenerative drug adjustment (30%), benzodiazepines, propofol, pre-status stage
both children disease (35%), surgery (6.7%), surgery, muscle paralysis by curare (n = 25; 37%),
and adults primary torsion dystonia metabolic disorders (5%), drugs, botulinum toxin, improved (n = 25;
(25.8%) failure of DBS device (5%) barbiturates, intrathecal baclofen 37%), worsened
(n = 11; 16.2%)
Grosso et al Retrospective N=3 11 y, all Cerebral palsy (n = 2), Febrile illness (n = 3) Pimozide, trihexyphenidyl, Improved
2012 female megalencephalic midazolam, baclofen, intrathecal
Italy13 leukoencephalopathy with and oral tetrabenazine
subcortical cysts (n = 1)
Touati et al Retrospective N = 10 11.4 y, 1:1 Primary dystonia (n = 2), Not mentioned Levodopa, anticholinergics, baclofen, Mortality 20% (n = 2/
2015, PKAN (n = 3), diazepam, clonazepam, 10), improved to
Tunisia19 cerebral palsy (n = 5) midazolam, chlorpromazine, pre-SD state (n = 8)
haloperidol, trihexyphenidyl
Combe et al Retrospective 13 y, 2:1 Intercurrent illness or infection Diazepam, baclofen, oral and Improved

(continued)

445
 Table 3. (continued)

446
Mean age (y)
at onset of
Author, year, dystonia,
population male: female
origin Type of study No. of patients ratio Underlying cause for SD Trigger Modalities used for treatment Outcome

2016, N = 3; 4 Dyskinetic cerebral palsy (n = (n = 2), intrathecal levodopa, midazolam,

UK11 episodes 3) none (n = 1) chloral hydrate
Nakou et al Retrospective N=5 11 y, 1:1.5 Dyskinetic cerebral palsy (n = Infection (n = 2), none (n = 2), IV clonidine, DBS, nitrazepam, Improved
2017, 2), removal of DBS due to midazolam, lorazepam, diazepam,
UK15 genetic epileptic erosion and infection (n = 1) and nitrazepam, propofol and
encephalopathy (n = 1), morphine infusions
unexplained
developmental delay and
microcephaly (post-DBS)
(n = 1),
PKAN (n = 1)
Nerrant et al Retrospective N = 40; 58 15.7 y, 1:1.1 Unknown (n = 10), Medication alterations (24%), DBS, other baseline medications Two deaths (5%),
2018, episodes (31 cerebral palsy (n = 6), DBS-related (60%) progressive
France16 pre-DBS and PKAN (n = 6), worsening over years
27 episodes Lesch-Nyhan (n = 4), (37.5%)
after DBS genetic encephalopathies/
onset) epilepsies (n = 7),
mitochondrial (n = 2),
glutaric aciduria (n = 1),
PLA2G6–associated
neurodegeneration (n = 1),
Niemann-Pick (n = 1),
others (n = 2)
Garone et al Retrospective N = 34; 63 9 y 11 mo, Cerebral palsy (n = 13), Infection (48%), Clonazepam, tetrabenazine, One death (3%),rest
2019, episodes 3.2:1 tubercular painful stimuli (36.5%) baclofen, oral and intrathecal improved
Italy12 meningoencephalitis trihexyphenidyl, lorazepam,
(n = 1), tizanidine, diazepam, gabapentin,
unknown cause (n = 6), haloperidol, risperidone,
GABRA1 related pimozide, pallidotomy
encephalopathy (n = 1),
GNAO1 encephalopathy (n
= 2),
sulfite oxidase deficiency (n
= 1),
neuronal ceroid
lipofuscinosis (n = 1),
sequelae to central
nervous system insult
(n = 3),
leukodystrophy (n = 3),
Dandy Walker syndrome
(n = 1),

(continued)
 Table 3. (continued)

Mean age (y)

at onset of
Author, year, dystonia,
population male: female
origin Type of study No. of patients ratio Underlying cause for SD Trigger Modalities used for treatment Outcome

bilateral striatal necrosis (n

= 2)
Narayan et al Retrospective N = 23; 33 Median age 6 Cerebral palsy (n = 8), Infection (n = 8; 35%), Midazolam, vecuronium, propofol, Improved (100%),
2020, episodes y, 1.2:1 autoimmune encephalitis drug-related (n = 2; 9%), trihexyphenidyl, clonidine, relapse (26%), no
India8 (n = 2), none (n = 13; 56%) tetrabenazine, melatonin, triclofos mortality
subacute sclerosing , gabapentin DBS
panencephalitis (n = 1),
aromatic l-amino acid
decarboxylase deficiency (n
= 1),
unknown (n = 2),
central nervous system
infection (n = 3),
genetic epileptic
encephalopathy (n = 1),
glutaric aciduria (n = 1),
PKAN (n = 1),
Wilson disease (n = 1),
primary dystonia (n = 1),
head trauma sequelae
(n = 1)
Current Retrospective, N = 24 6.3 y, 3:1 Cerebral palsy (n = 8), Intercurrent illness/infection (n Trihexyphenidyl, diazepam, oral Deaths (n = 3; 12.5%)
study, single center tubercular meningitis with = 18; 75%), not known (n = baclofen, midazolam, clonazepam
2021, India complications (n = 3), 3; 12.5%), progression of and clobazam, gabapentin,
hypoxic injury to the brain underlying disease (n = 2; melatonin, clonidine,
(n = 2), 8.3%), drug-induced or orazepam, levodopa,
autoimmune encephalitis withdrawal (n = 1; 4.2%) tetrabenazine, triclofos
(n = 1),
cortical venous thrombosis
(n = 1),
mitochondrial (n = 3),
neuro-Wilson (n = 2),
PKAN (n = 2),
suspected organic acidemia
(n = 1) Primary progressive
dystonia (n = 1)

Abbreviations: DBS, deep brain stimulation; PKAN, pantothenate kinase-associated neurodegeneration; SD, status dystonicus.

447
448
vulnerable to recurrent episodes of status dystonicus because of
their pathologic lesions in the basal ganglia and propensity for
infection due to limited mobility.4,21 Other brain areas including
the cerebellum, brainstem, and the sensory cortex can be the
cause of dystonia because of their complex connections with
the basal ganglia and may show sparing of the latter on neuro-
imaging, as seen in the one-third of cases in our cohort.24,25 The
preexisting neurologic manifestations should guide the appro-
priate flow of neuroimaging, metabolic, and genetic investiga-
tions in cases where the cause of status dystonicus is not
established.
A triggering factor was identified in 88% of our cases.
Triggers are identifiable in 50% to 66% of the cases in children
and are commonly either intercurrent infections or drug adjust-
ments.4,7,8 It is important to avoid abrupt withdrawal or change
in commonly implicated medications such as tetrabenazine, clo-
nazepam, baclofen, and haloperidol as several children with an
underlying neurologic illness are already using these medica-
tions at the baseline. Other reported triggers include pain,
surgery, reflux disease, sleep disturbance, calculi, or constipa-
tion.9 It may be difficult to determine whether the fever is the
cause or effect of persistent dystonic contractions or autonomic
features. Laboratory parameters of inflammation may help iden-
tify an antecedent infection. Akin to status epilepticus and other
metabolic crises, it would be prudent to give a broad-spectrum
antimicrobial till infection is completely excluded. It is impor-
tant to include these aspects in the parental counseling and
chronic care plan of these children.
Our study highlights several complications and a high mor-
tality rate (12.5%) in children with status dystonicus. This is
similar to the mortality reported in literature (10%-20%).19,26
The episodes of status dystonicus and the immediate recovery
period can be unpredictable, varying between recoveries to
rebound status to death. The muscle spasms during status dystonicus
can cause respiratory compromise and severe metabolic distur-
bances, particularly rhabdomyolysis (indicated by rising muscle
enzymes such as CPK, and liver enzymes) and acute renal failure.
Both these complications were most common in our cohort. The
pharyngeal or laryngeal spasm, bulbar weakness, aspiration pneu-
monia, compromised chest wall expansion from diaphragmatic or
truncal dystonia, or respiratory depression from exhaustion, potenti-
ated by medication use contribute to poor airway maintenance in
children with status dystonicus.9 Bulbar and respiratory dysfunction
are often considered essential features of status dystonicus.5 The
initial investigations and management should always be directed
to detect and manage these complications.
The ABCD approach to the management of status dystoni-
cus includes Addressing triggers (in addition to Airway),
Beginning supportive measures (in addition to Breathing),
Calibrating sedation (in addition to Circulation and checking
for the above-mentioned Complications), and administering
Dystonia-specific drugs.26 The pharmacologic management
including antidystonia (anticholinergic or dopamine pathway
medications) and muscle-relaxant drugs often begins simultane-
ously.7 In our cohort, oral trihexyphenidyl followed by oral or
intravenous diazepam, oral baclofen, and midazolam infusion
Journal of Child Neurology 37(6)
were the most common initial choices. Trihexyphenidyl had
been started in these cases to control dystonia on an outpatient
basis and was continued as an antidystonia drug during the
crisis, with dose escalation. When the intravenous drugs were
tapered off at the end of the status dystonicus, it was continued
as a maintenance drug. Trihexyphenidyl is a centrally acting
muscarinic receptor antagonist frequently used in the manage-
ment of generalized dystonia, with variable efficacy.27 The
exact mechanism of antidystonia action is not known but prob-
ably is related to the rebalancing of cholinergic to dopaminergic
interneuronal drive in the basal ganglia and its related net-
works.28 It has been suggested that younger children with extra-
pyramidal cerebral palsy are more likely to respond to the
medication, and its primary benefits are improved upper limb
function and expressive language, especially in the absence of
spasticity and severe cognitive impairment.29,30 More recent
evidence on the use of trihexyphenidyl suggest that it has
limited efficacy in children with cerebral palsy and dystonia.
A Cochrane review on the use of trihexyphenidyl in people
with dystonia and cerebral palsy found insufficient evidence
(based on a single randomized study on 16 children) regarding
its effectiveness for reducing dystonia, or improving upper limb
function.31 Although there was low-quality evidence that the
drug may improve participation in activities of daily living, yet
there was an increased risk of adverse effects such as agitation,
constipation, dry mouth, and poor sleep.31 A recent systematic
review of pharmacologic and neurosurgical interventions for man-
aging dystonia in cerebral palsy concluded that trihexyphenidyl
may have little or no effect on dystonia, motor function, ease of
caregiving, individualized goal achievement, and quality of life
and may increase the risk of adverse events (based on 1 random-
ized and 6 nonrandomized studies).32 The benefits of trihexyphe-
nidyl are often not dramatic and may take several days to be fully
effective. In the clinical scenario, it is more common to start trihex-
yphenidyl for dystonia on an outpatient basis and then continue
during emergent status dystonicus. Additionally, it may also be
started as add-on maintenance medicine prior to discharge.12
There are anecdotal reports on the beneficial effect of trihexyphe-
nidyl in acute life-threatening episodes because of a dystonic
movement disorder in secondary dystonia.33 It has been used in
the acute management of status dystonicus as a dystonia-specific
medication in one-fifth of the cases12 and has been suggested as
part of initial oral polytherapy.9 This may be due to the fact that
the drug is rapidly absorbed from the gut following oral adminis-
tration and the onset of action occurs within 1-2 hours. Additional
research is needed to evaluate the role of trihexyphenidyl in emer-
gent dystonia in children with secondary dystonia.
Midazolam infusion is often the cornerstone of manage-
ment in worsening cases, especially in nonintensive settings.8
Continuous intravenous midazolam (type A GABAergic
agent) via infusion pumps is usually chosen because of its
spinal interneuron blocking action, muscle relaxant effect,
weak depressant effect on the cardiovascular system, rapid
onset of action, and short half-life.9 Sleep and reduction of
pain are recognized relieving factors for movement disorders.
Hence, sedation and analgesia should be important
Saini et al
components of pharmacologic management.34 Other agents
that have been used include levodopa, haloperidol, gabapen-
tin, chlormethiazole, carbamazepine, valproate, and botuli-
num toxin.7,14 Antihypertensive drug clonidine (short-acting
α-2 receptor and imidazoline receptor agonist) is being
increasingly used to control dystonic spasms and restore
sleep in status dystonicus.12 Its main advantages are the lack
of respiratory depressant effect, availability of both oral and
parenteral routes, and suitability for use as chronic antidysto-
nia therapy after recovery from status dystonicus. Intravenous
doses as high as 9 μg/kg/h have been associated with reduced
use of benzodiazepines, morphine, and propofol, thus avoid-
ing severe hypotension or respiratory depression.15
Clonidine was used in one-third of our cases and did not
show any severe adverse effect to warrant drug discontinua-
tion. Although not as clearly defined as refractory status epi-
lepticus, a “refractory status dystonicus” needs more
aggressive treatment including general anesthesia, muscle
paralysis, and deep sedation in an intensive care setting.7,14
Antidystonia strategies may vary according to the expertise
and facilities available at different centers. It has been sug-
gested that antidystonia drugs, if already are ongoing and
proved effective, should be rapidly titrated to the highest tol-
erated dose or their introduction should be promptly consid-
ered if never tried previously.12 Intrathecal baclofen, deep
brain stimulation, pallidotomy, and thalamotomy are being
increasingly tried in refractory status dystonicus.16,35 A
recent meta-analysis on deep brain stimulation in pediatric
status dystonicus showed significant resolution in the acute
stage.36 None of the cases in our cohort could be subjected
to deep brain stimulation or pallidotomy owing to the financial
and technical limitations at the time of the study. Owing to the
retrospective nature of the study, the onset and duration of
each therapy during each subject’s inpatient stay could not
be noted. Also, status dystonicus has not received the same
attention as status dystonicus or status asthmaticus where the
end points are more clearly defined and the response to treat-
ment is binary (ie, if there is seizure or not). Although there is
significant treatment variability in our study, the effective
management strategies appear to be the use of oral or intrave-
nous benzodiazepines. Also, the use of clonidine was not asso-
ciated with significant side effects portending drug
discontinuation. Prospective studies with clear documentation
of the timing of drug initiation and reduction of severity of
dystonia are needed to make definitive recommendations.
In conclusion, status dystonicus is a neurologic emergency
in children with severe dystonia that is associated with signifi-
cant complications and a high mortality rate. Static and acquired
disorders are more common than heredo-familial causes.
Identification and treatment of infection in children is important
as the majority of cases are triggered by an intercurrent infec-
tion. The initial choice of pharmacologic agents includes trihex-
yphenidyl, diazepam, baclofen, and continuous intravenous
midazolam via infusion pumps. Addition and rapid titration
of doses of sedatives and muscle relaxants are often required
to achieve prompt resolution of the dystonic spasms.
449
Prospective studies in larger cohorts are needed to assess the
effectiveness of therapies and long-term management plans,
including surgical interventions.
Author Note
A part of the study data was presented at the International Child
Neurology Conference (ICNC) 2018, India, and 27th Annual
Conference of Indian Academy of Neurology (IANCON-2019), India.
Author Contributions
AGS: plan of the study, data collection, original draft of manuscript,
review of literature; IH: data collection and draft of manuscript; KG:
data collection and draft of manuscript; JM: intensive care manage-
ment of the patients and approval of the study; SD: data collection
and approval of the study; RS, LS, JS, NS: patient management and
approval of the manuscript; PS: final approval of the study and guaran-
tor of the manuscript.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the
research, authorship and/or publication of this article: AGS and NS
have received research grants from PGIMER and SERB.
Ethics Approval
The ethics committee at the Postgraduate Institute of Medical
Education and Research approved the study (NK/5651/756).
ORCID iDs
Arushi Gahlot Saini https://orcid.org/0000-0002-5747-8975
Lokesh Saini https://orcid.org/0000-0003-3153-0736
Renu Suthar https://orcid.org/0000-0002-7003-7218
Jitendra Sahu https://orcid.org/0000-0001-5194-9951
Naveen Sankhyan https://orcid.org/0000-0003-4929-1163
Pratibha Singhi https://orcid.org/0000-0002-3238-3670
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