Download Status Dystonicus Guidelines

Status Dystonicus Guidelines
Great Ormond Street Hospital for Children NHS Trust
Status dystonicus – definition:
‘Increasingly frequent and severe episodes of generalized dystonia (sustained involuntary
muscle contraction leading to abnormal postures and movement) which requires urgent
hospital admission’1. Status dystonicus can occur in the context of an acute illness
affecting the central nervous system e.g. hypoxic ischaemic /infective / metabolic
encephalopathies or may occur in children with known chronic dystonia (either primary
or secondary). The latter group may be particularly difficult to treat and may require
prolonged periods of hospitalization.
Goals of treatment for children with status dystonicus:
Many children presenting to the Neurology Unit at Great Ormond Street Hospital have
dystonia. These guidelines are for use in those children who have severe and
unremitting dystonic spasms that requires inpatient management of associated
medical complications and pain. Clear treatment goals should be established for these
children before pursuing approaches that may include heavy sedation, muscle paralysis
etc. Goals of treatment are usually those of achieving comfort and medical stability rather
than improving function.
Triggers that can exacerbate chronic dystonia, precipitating status dystonicus:
 pain from any source
- GIT esp. gastro-oesophageal reflux, constipation
- dental (ulcers, caries)
- orthopaedic e.g. dislocated hip, casting, fractures
 intercurrent illness / infection
 weaning or addition of some drugs
 surgical procedures and anaesthetics
 other stressors
Medical complications of status dystonicus:
 Elevated body temperature
 Pain
 Exhaustion from sleep deprivation and exertion
 Rhabdomyolysis leading to myoglobinaemia and raised CPK
 Dehydration with electrolyte disturbance from excess sweating
 Acute renal failure as a consequence of myoglobinuria / dehydration
 Bulbar dysfunction with risk of pulmonary aspiration
 Respiratory insufficiency
 Death
INITIAL ACTION:
The patient’s immediate medical state needs to be assessed and managed:
1. Airway compromise: Dystonia may compromise the airway through respiratory
muscle spasm leading to alveolar hypoventilation or through vocal cord adductor
spasm leading to stridor. In addition, dysfunction of pharyngeal muscles may lead
to an increased risk of pulmonary aspiration. Many of the sedative drugs used to
treat status dystonicus may compound this problem. Patients should be closely
monitored for chest symptoms and signs and if present, oxygen saturation should
be monitored, a CXR performed and arterial gases measured. Oral feeding may be
contra-indicated in some children and feeding via a naso-gastric or naso-jejunal
tube may be preferable.
2. Rhabdomyolysis and myoglobinaemia: Myoglobin levels (urine dipstick
positive for blood in the absence of red blood cells on urine microscopy,
confirmed by plasma levels though results take days) and CPK levels (plasma)
should be measured in all patients with status dystonicus and repeated 24 and 48
hours later as rise in CPK may take 24-28hrs. See guidelines.
3. Hydration: Increased insensible losses through sweating can rapidly lead to
dehydration and maintenance fluids may need to be increased by an additional 520% each day to compensate for increased insensible losses. Electrolytes should
be measured regularly.
4. Renal compromise: This occurs as a consequence of dehydration and/or
myoglobinuria following rhabdomyolysis.
5. Pain /distress: Seek any cause of pain which may exacerbate dystonia (see
above) and treat actively. Dystonic spasms may also be painful and appropriate
analgesia (paracetamol, non-steroidal analgesics, codeine) should be given.
INITIAL MANAGEMENT OPTIONS:
Pharmacological (drug doses can be obtained here)
1) Sedation and muscle relaxation: A number of sedatives (triclofos or chloral and
trimeprazine) and/or muscle relaxants (oral/rectal diazepam, buccal/iv midazolam, iv
lorazepam) may be useful alone or in combination to provide relief from painful and
exhausting spasms and allow periods of sleep. Extreme care should be taken to monitor
children when using combinations of drugs with sedating properties.
2) Heavy sedation / muscle relaxation: This may be required in some children for
medical stability. Intravenous midazolam or chlormethiazole may be used.
Chlormethiazole has the advantage that it is less of a respiratory depressant than
midazolam and can be weaned to titrated oral doses. Midazolam has a long half-life,
allowing slow weaning. It also has a spinal interneuron blocking action, of benefit in
children with dystonia. Levels of sedation achieved with these drugs requires close
monitoring of cardiovascular and respiratory function, and this may necessitate PICU
admission.
3) Indications for paralysis and intubation include:
 Airway compromise / respiratory failure
 Exhaustion / severe discomfort despite maximal sedation and muscle
relaxants
 Metabolic compromise e.g. renal failure requiring haemodialysis (relative
indication)
Non pharmacological and supportive approaches:
1) Addressing any known triggers: There are many triggers that can underlying an
episode of status dystonicus (see above). These should be actively sought by thorough
careful history and examination of the child and targeted investigation. Adequate
analgesia should be provided for pain.
2) Address emotional / behavioural /psychological contributing factors: Many
children with dystonia may be quite physically disabled but with intact cognition. In
some of these children psychological / emotional factors can further aggravate their
underlying dystonia. This should be considered and appropriate support provided.
3) Positioning and handling: Positioning can be useful in ‘breaking’ the spasming in
some children and nursing and physiotherapy input may provide additional strategies to
improve spasm-free periods and sleep. In some children, dystonia may be exacerbated by
handling and this should be minimised to necessary cares.
SUBSEQUENT APPROACH:
Once the patient’s medical condition has been initially stabilised the following points
need to be considered:
1. Document the site and severity of dystonia:
It is important that this is clearly described in the patients notes as this provides the
means to objectively assess if improvement or deterioration is occurring over time e.g.
with the trial of a particular drug. Charts for documenting site and severity of dystonia
using objective scales2 are provided here.
2. What is the likely aetiology of the underlying dystonia? (NB careful clinical and
family history)





Consider the possibility of drug-induced dystonia:
 Neuroleptic Malignant Syndrome due to antidopaminergics (including
tetrabenazine, haloperidol, sulpiride), anticholinergics and also reported with
sudden levodopa withdrawl.
 Reported with the use of carbamazepine and metaclopramide.
primary (dystonia is the sole clinical sign +/-tremor)
secondary (identifiable cause of dystonia, see investigations below)
dystonia plus syndrome (with other neurological features e.g. dystonia-myoclonus
syndrome, dopa-responsive dystonia with parkinsonism)
dystonia as part of a heredodegenerative disease (e.g. Wilson’s disease, X-linked
dystonia-parkinsonism, see investigations below)
3. What targeted investigations should be considered (depending on clinical / family
history) to clarify the aetiology?












Blood: FBC, vacuolated white cells, reticulocytes, wet blood film for acanthocytes,
U+E’s, LFT’s, calcium, magnesium, phosphate, uric acid, copper and ceruloplasmin,
autoantibodies screen, amino acids, lactate, purines and pyramidines, lysosomal
enzymes (hexosaminidase, arylsulphatase, fucosidase, β-galactosidase), acylcarnitine
species, cholesterol, triglycerides, lipoprotein strip and transferrin isoelectric
focussing
ABC serology (depending on clinical history)
Molecular genetics (depending on clinical / family history) :
- DYT1 (DYT1 gene mutation in idiopathic torsion dystonia)
- DYT5 mutation in dopa responsive dystonia)
- PLP
- SCA6
- DRPLA (relevant if of Japanese origin, or family history)
- Huntington (consent a significant issue, councelling required)
(NB: discuss with clinical geneticist if appropriate and obtain and document
parental consent in the patients notes)
Urine amino and organic acids, HVA, uric acid, copper, sulphite, oligosaccharide
and mucopolysaccharide screen
CSF microscopy, biochemistry, lactate, amino acids, amine neurotransmitter
metabolites and pterin species
Muscle biopsy for histopathology, histochemistry and respiratory chain enzymes
Rectal biopsy (full thickness not suction) for intraneuronal storage material seen in
the gangliosidoses, neuronal intranuclear inclusion disease (NINID) and Batten’s.
Skin biopsy for fibroblast culture and EM of nerves
Bone marrow biopsy
Slit-lamp examination (for K-F rings)
VEP/ERG, ENMG/NCV, EEG
MRI
SUBSEQUENT MANAGEMENT OPTIONS:
Specific pharmacological therapy aimed at reducing severe dystonia (drug doses):
The pharmacological control of severe generalized dystonia is difficult and inpatient
management is largely centred on sedation, muscle relaxation and supportive care.
Children with new onset dystonia in the context of an acute CNS illness usually improve
over time and may be managed expectantly. Children with status dystonicus on a
background of known chronic dystonia are often more difficult to manage. In such
children the risks of complications from the severe dystonia need to be carefully
measured against the risk of side-effects from the high doses of specific anti-dystonia
drugs often required. Decisions regarding the management of such children and use of
these drugs should be made in conjunction with a Consultant Paediatric Neurologist and
patients should be closely monitored for efficacy of treatments using objective dystonia
scales and serial video. The following are general guidelines for treatment options:
1. Levodopa should be tried in all children with idiopathic primary dystonia and
considered in other cases. Levodopa trial should be continued for 3 months and
increased to maximum doses before being discontinued.
2. In children with severe and disabling dystonia, the next option is a slow escalation
of trihexyphenidyl (benzhexol) to high dose or until side effects (anticholinergic
e.g. urinary retention, blurred vision, GI upset) intervene. If side effects emerge
then reducing the dose and maintaining it at a reduced level for 1 month before
increasing again, may allow greater tolerability of higher doses.
3. In children in whom the above drugs have been ineffective, there is little clear
evidence in previous literature to guide the next approach. Tetrabenazine (used
at low doses because of side effect of significant depression) in combination with
either sulpiride or haloperidol may be added to trihexyphenidyl (benzhexol). If
extra-pyramidal side-effects (parkinsonism, akathisia) emerge using sulpiride /
haloperidol then increasing the dose of trihexyphenidyl (benzhexol) may alleviate
these and allow for further increases in sulpiride / haloperidol. Sulpiride /
haloperidol have the long term potentially irreversible side effect of tardive
dyskinesia.
4. There are case reports of a number of other drugs being useful in children with
status dystonicus.
5. In children with intractable severe dystonia, referral for deep brain stimulation
may also be a consideration.
Dr Kate Riney / Prof Robert Surtees / Dr Carlos deSousa
21/05/2004
References:
1. Manji H, Howard RS, Miller DH et al. Status dystonicus: the syndrome and its
management. Brain 1998;121:243-252.
2. Barry MJ, VanSwearingen JM, Albright AL. Reliability and responsiveness of the
Barry-Albright dystonia scale. Dev Med Child Neurol 1999; 41: 404-411.
3. Jankovic J, Penn AS. Severe dystonia and myoglobinuria. Neurology
1982;32:1195-7.
4. Marsden CD, Marion MH, Quinn N. The treatment of severe dystonia in children
and adults. J Neurol Neurosurg Psychiatry 1984;47:1166-73.
5. Vaamonde J, Narbona J, Weiser R et al. Dystonic storms: a practical management
problem. Clin Neuropharmacol 1994;17:344-7.
6. Kyriagis M, Grattan-Smith P, Scheinberg A et al. Status dystonicus and
Hallervorden-Spatz disease: treatment with intrathecal baclofen and pallidotomy.
J Paediatr Child Health 2004;40:332-5.
Renal guidelines for the management of rhabdomyolysis
Diagnosis of rhabdomyolysis is difficult:
 No relationship between severity of disease and CPK levels
 Myoglobin levels rapidly rise during injury, then fall within 6 hours, CPK is slow to
rise (2-12 hrs after injury, peaks 24-72hrs later)
Consequences of rhabdomyolysis:
 Myoglobinaemia (rarely measured)
 Myoglobinuria : Positive urine dipstick for blood, few or no red
cells on microscopy, specific analysis (send to lab, takes days)
 Elevated CPK (MM band)
 Other electrolyte disturbance
 Increased potassium
 Increased phosphate
 Decreased calcium
 Increased urate
 hypoglycemia with pancreatic dysfunction
Management of rhabdomyolysis:
 Make the diagnosis (raised CPK (late), test urine (see above))
 Manage the patient on the basis of electrolytes and not CPK.
 Seek advice from renal team if acute renal failure
 If urine output is reasonable (> 0.5 ml/kg/hr):
 high fluid input = 3 l/m2/day (0.45% saline/2.5% dext)
 add sodium bicarbonate to fluids, aim for urine pH >7
(start with 10mmol sodium bicarbonate / 500ml)
 If oligoanuric:
 consider first a fluid challenge (5-10ml/Kg), possibly with
frusemide to establish urine output
 if unsuccessful, dialyse for severe electrolyte disturbance
(CVVH should clear myoglobin reasonably well, but no
real data in children)
 Monitor BM’s
Drug
Chloral hydrate
Doses
30-50mg/kg (max 1g/dose) tds
(can be given rectally)
Triclofos
Dose depends on age / weight
See Guys and St Thomas formulary
DO NOT USE WITH CHLORAL as
both derivatives of the same drug
2mg/kg/dose (max 60mgs) max BD
(caution with use < 6 months)
Alimemazine (Trimeprazine,
Vallergan)
Diazepam oral and rectal
Clomethiazole oral
(Chlormethiazole)
Midazolam buccal
(use iv preparation)
Lorazepam iv
Midazolam iv
RECTAL (PRN: can repeat dose x1)
<1yr 2.5mg PR
1-3yrs 5mg PR
>3 yrs 10mg PR
ORAL
<1yr 250micrograms/kg BD
1-4 yrs 2.5mg BD
5-12 yrs 5mg BD
>12 yrs 10mg BD
20mg/kg/day (of edisylate) given in
divided doses every 2-4 hours
500microgram/kg (max 10mgs)
sublingual
Used PRN
50 micrograms/kg/dose (max 4mgs)
Can repeat x1 if required
Max dose of 0.1mg/kg or 8mgs in 12
hours
Slow iv injection of 100200microgram/kg then infusion of
30microgram/kg/hr increasing
according to response
Clomethiazole iv
(Chlormethiazole)
5-10mgs(0.6-1.25 mls of 0.8%
solution)/kgs/hr. Titrate up every 24hrs to achieve response (max 18mgs
or 2.25mls/kg/hr).
Wean dose every 4-6hrs
Levodopa
All doses quoted are for the
levodopa component of Sinemet
Sinemet-62.5 (carbidopa 12.5mg,
levodopa 50mgs): start 1mg/kg/d
(unless <1yr: 0.25mg/kg/d)
increasing to max dose 10mg/kg/d
Once total dose of levodopa is
Side Effects to look for
Gastric irritant, Rash, Headache
Ketonuria
Eosinophilia, low WCC
Derivative of chloral hydrate.
Same side effects but less
gastric irritation
Antimuscarinic effects (urinary
retention, dry mouth, GI
disturbance)
Extrapyramidal effects
Mood change, irritability
Liver dysfunction
Arrythmias
Long half life
Doses may be cumulative
Drowsiness, irritability
Respiratory depression
Tolerance may occur
Tachyphylaxis occurs quickly
See below
Respiratory depression
Hypotension
S/P Liver disease
Respiratory depression
Cardiovascular depression
(severe hypotension)
Potentiated by erythromycin
and other drugs
Increased respiratory tract
secretions /irritation
Rash, GI upset
Cardiovascular depression
Respiratory depression (esp
with longer infusions)
Plastic giving sets must be
changed every 24hrs
Contains high sodium content
GI upset
Sleep disturbance
Hypotension, arrhythmias
Red urine
Psychiatric manifestations
Trihexyphenidyl (Benzhexol)
Tetrabenazine
Sulpiride
Haloperidol
>100mgs/d switch to Sinemet-110
(10mgs carbidopa, 100mgs levodopa)
as less carbidopa is preferable.
Start 1mgs TDS (<8yrs) or 2mgs
TDS (>8yrs). Increase total dose by
1mg (<8yrs) or 2mgs (>8yrs) every 7
days until clinical effect or side
effects intervene or max dose 10mgs
TDS
<4yrs start 6.25mgs OD
>4yrs start 12.5mgs OD, increasing
to 12.5mgs TDS
Adolescent start 25mgs OD
increasing to 25mgs TDS
If >8yrs 50mgs BD, increment total
dose by 50mgs to max 100mgs BD
If <8yrs (use haloperidol in
preference as doses better described)
25mgs BD, increment total dose by
25mgs to max 50mgs BD
12.5-25 micrograms/kg BD (max
10mg/d) further increase under
guidance from Paediatric Neurologist
Peripheral neuropathy
Anti-cholinergic effects
(urinary retention, dry mouth,
dry eyes, blurred vision, Gi
disturbance etc.)
Onset of action can be delayed
for months
Depression which may be
severe with suicidal ideation
Drowsiness at higher doses
Extrapyramidal signs
Tardive Kinesia
Extrapyramidal signs
Tardive Kinesia
Barry-Albright Dystonia Scale
(Barry MJ, VanSwearingen JM, Albright AL. Reliability and responsiveness of the Barry-Albright dystonia scale. Dev Med Child
Neurol 1999; 41: 404-411)
This scale produces a reliable total score for children with generalized dystonia, but reliability of scores of
individual regions is less. To enhance reliability in scores with repeated measures, this scale should
preferably be used by someone with experience in assessing the child with dystonia and scored following
observation of the child and review of a structured video (suggestions for video structure are given below
the scores for each region being assessed)
Patients Name:
Hospital Number:
Date of Assessment:
If this is a repeat assessment, please indicate the reason for reassessment:
Assessor:
Assessors position (medical, physio, OT):
Video taken with parental consent: Y / N
If yes, location where video stored for future reference:
Directions: Assess the patient for dystonia in each of the following regions: eyes, mouth,
neck, trunk, each upper and lower extremity (8 body regions). Write the scores on the
lines provided. Rate severity based only on dystonia as evidenced by abnormal
movements or postures. When assessing functional limitations, do not score as dystoniainduced functional limitation if other factors, such as weakness, lack of motor control,
cognitive deficits, persistent primitive reflexes, and/or other movement disorders are
contributing to functional limitation.
Definitions of movement disorders:
- Dystonia: sustained muscle contractions caused by twisting
and repetitive movements or abnormal postures
- Spasticity: Velocity-dependent resistance to passive
movement
-
Athetosis: Distal writhing or contorting movements
Chorea: Brief, rapid, unsustained, irregular movements
Ataxia: Incoordination of movement characterized by widebased unsteady gait, flailing movements.
Eyes: signs of dystonia of the eyes include: prolonged eyelid spasms and/or forced eye
deviatons
0- Absent
1- Slight: dystonia less than 10% of the time and does not interfere with tracking
2- Mild: frequent blinking without prolonged spasms of eyelid closure, and/or eye
movements less than 50% of the time
3- Moderate: prolonged spasms of eyelid closure, but eyes open most of the time,
and/or eye movements more than 50% of the time that interfere with tracking, but
able to resume tracking
4- Severe: Prolonged spasms of eyelid closure, with eyelids closed at least 30% of
the time, and/or eye movements more than 50% of the time that prevent tracking
*- Unable to assess eye movements
(Suggest video eyes and upper face (at rest and with eyes open and closed if possible)
for minimum of 2 minutes followed by period of video of the patient visually fixing
on and then tracking an object / face)
Eyes scored ______
Mouth: signs of dystonia of the mouth include grimacing, clenched or deviated jaw,
forced open mouth, and/or forceful tongue thrusting
0- Absent
1- Slight: dystonia less than 10% of the time and does not interfere with speech
and/or feeding
2- Mild: dystonia less than 50% of the time and does not interfere with speech and/or
feeding
3- Moderate: dystonia more than 50% of the time and/or dystonia that interferes with
speech and/or feeding
4- Severe: dystonia more than 50% of the time and/or dystonia that prevents speech
and/or feeding
*- Unable to assess mouth movements
(Suggest video of mouth for minimum of 2 minutes followed by period of speech
(reading, conversation and sounds ‘tee’, ‘mee’, ‘la’, ‘ka’ and prolonged holding of
‘eeeeeee’), tongue protrusion and feeding solids/liquids if safe)
Mouth scored______
Neck: signs of dystonia of the neck include pulling of the neck into any plane of motion:
extension, flexion, lateral flexion or rotation
0- Absent
1- Slight: pulling less than 10% of the time and does not interfere with lying, sitting,
standing and/or walking
2- Mild: pulling less than 50% of the time and does not interfere with lying, sitting,
standing and/or walking
3- Moderate: pulling more than 50% of the time and/or dystonia that interferes with
lying, sitting, standing and/or walking
4- Severe: pulling more than 50% of the time and dystonia that prevents sitting in a
standard wheelchair (e.g. requires special head rest), standing and/or walking
*- Unable to assess neck movements
(Suggest AP and lateral video of neck at rest with head unsupported for minimum of
2 minutes each view, then if possible ask to move neck in all planes and to sit, stand,
walk)
Neck scored______
Trunk: signs of dystonia of the trunk include pulling of the trunk into any plane of
motion: extension, flexion, lateral flexion or rotation
0- Absent
1- Slight: pulling less than 10% of the time and does not interfere with lying, sitting,
standing and/or walking
2- Mild: pulling less than 50% of the time and does not interfere with lying, sitting,
standing and/or walking
3- Moderate: pulling more than 50% of the time and/or dystonia that interferes with
lying, sitting, standing and/or walking
4- Severe: pulling more than 50% of the time and dystonia that prevents sitting in a
standard wheelchair (e.g. requires adapted seating system), standing and/or
walking
*- Unable to assess trunk movements
(Suggest AP and lateral video at rest with trunk unsupported for minimum of 2
minutes each view, then if possible ask to move trunk in all planes and to sit, stand,
walk)
Trunk scored______
Upper extremities: signs of dystonia of the upper extremities include sustained muscle
contractions causing abnormal postures
0- Absent
1- Slight: dystonia less than 10% of the time and does not interfere with normal
positioning and/or functional activities
2- Mild: dystonia less than 50% of the time and does not interfere with normal
positioning and/or functional activities
3- Moderate: dystonia more than 50% of the time and/or dystonia that interferes with
with normal positioning and/or upper extremity function
4- Severe: dystonia more than 50% of the time and/or dystonia that prevents normal
positioning and/or upper extremity function (e.g. arms restrained to prevent
injury)
*- Unable to assess upper extremity movements
(Suggest video of each upper limb at rest for minimum 30 seconds followed by video
of positoning (ability to sustain?) and attempt at basic functional activity e.g. holding
object, releasing object, touching object, drawing)
Left upper limb scored________
Right upper limb scored_______
Lower extremities: signs of dystonia of the upper extremities include sustained muscle
contractions causing abnormal postures
0- Absent
1- Slight: dystonia less than 10% of the time and does not interfere with normal
positioning and/or functional activities
2- Mild: dystonia less than 50% of the time and does not interfere with normal
positioning and/or functional activities
3- Moderate: dystonia more than 50% of the time and/or dystonia that interferes with
with normal positioning and/or lower extremity weight bearing and/or function
4- Severe: dystonia more than 50% of the time and/or dystonia that prevents normal
positioning and/or lower extremity weight bearing and/or function
*- Unable to assess lower extremity movements
(Suggest video of each lower limb at rest for minimum 30 seconds followed by video
of positoning (ability to sustain?) and attempt at basic functional activity e.g. sitting,
standing (front, back and lateral view), walking towards and away, tapping floor with
ball and heel of foot)
Left lower limb scored________
Right lower limb scored_______
TOTAL SCORE _________
Site (please circle which is most suitable for patient at time of scoring):

segmental dystonia - two or more adjacent focal areas, usually head and neck,
trunk and arm(s)

hemi-dystonia (arm and leg affected on the same side)

multifocal dystonia - two or more separate focal areas affected

generalised dystonia - widespread dystonia
Please document level of pain and distress at time of scoring (from standardized pain
assessment charts): None, Mild, Moderate, Severe.
Please document medication and doses at time of scoring:
Medical Team to document relevant information re medical status which may affect
scoring (please tick):




Respiratory / Bulbar compromise
o Frequent desaturations
o Increased feeding support (e.g. NGT)
o Recent aspiration pneumonia
o Abnormal arterial gases
o Ventilatory support (supplemental oxygen / pressure support)
Metabolic disturbance
o Abnormal renal chemistry
o Renal support with dialysis
o Myoglobinaemia /myoglobinuria
o Dehydration
o Hypoglycemia
Cardiac / Circulatory dysfunction
o Hypotension
o Abnormal heart rate / rhythm
Other
If side-effects have been experienced from any drugs used as part of these guidelines (for
list of common side-effects see here.
If patient score or medical status changed from previous score please indicate how and
why this is thought to be the case:
Review of previous literature reports of management of status dystonicus:
Authors
Jankovic and
Penn, 19823
Number of patients
1
(rhabdomyolysis, renal
failure)
Marsden et al.,
19844
2 patients ( 12y and
15y)
Vaamonde et al.,
19945
1 patient
Tetrabenazine
Pimozide
Benzhexol
Diazepam
Baclofen
Haloperidol
Carbamazepine
Valproate
Primidone
Muscle paralysis
1 patient
Chlorpromazine
Haloperidol
Pimozide
Diazepam
Benzhexol
Progabide
Tetrabenazine
Baclofen
Muscle paralysis
Chlormethiazole iv (3/5)
Midazolam iv
Clonazepam iv/po
Muscle paralysis (4/5)
Tetrabenazine
Pimozide
Benzhexol
Valproate
Primidone
Propranolol
Diazepam
Baclofen (po/it)
Haloperidol
Acetazolamide
Botulinum toxin
Baclofen
Baclofen
Intrathecal
Manji et al.,
19981
Kyriagis et al.,
5 children aged 5-14yrs
presenting over a 10
year period, one had
rhabdomyolysis with
CK 43,000 and renal
failure
1 patient with
Medications used
Haloperidol
Benzhexol
Carbamazepine
Levodopa
Ethopropazine
Baclofen
Tetrabenazine
Muscle paralysis
Tetrabenazine Pimozide
Benzhexol
(1 required paralysis and
ventilation)
? Effective drugs
? transient
improvement
with baclofen
and
tetrabenazine
Comments
Child later underwent
bilateral thalamotomy
One child
responded, 1 had
no response and
an additional
dystonic reaction
with pimozide
None
75% of adults improved
on this regimen but
depression was a
significant side-effect.
High dose
benzhexol
worked in one
child
Acetazolamide
and haloperidol
worked in one
child
Intrathecal
baclofen and
thalamotomy did
not work
This patient died
shortly after admission
2/5 died, 2/5 were
worse (than their precrisis state), 1/5
returned to his precrisis state. All had
prolonged admissions
Several triggers for
exacerbating dystonia
identified in these
children
Pimozide was
associated with
significant cardiac
toxicity in 2/5 children
This patient died
20046
Hallervorden-Spatz
Diazepam
Tetrabenazine
Haloperidol
Benzhexol
Levodopa
Biotin
Morphine
Intrathecal baclofen
Chloral Hydrate
Pallidotomy
baclofen
Pallidotomy
15months after
discharge