Status Dystonicus GuidelinesGreat 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 stressorsMedical 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 5-20% 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 deSousa21/05/2004

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 Doses Side Effects to look for

Chloral hydrate 30-50mg/kg (max 1g/dose) tds(can be given rectally)

Gastric irritant, Rash, HeadacheKetonuriaEosinophilia, low WCC

Triclofos Dose depends on age / weightSee Guys and St Thomas formularyDO NOT USE WITH CHLORAL as both derivatives of the same drug

Derivative of chloral hydrate. Same side effects but less gastric irritation

Alimemazine (Trimeprazine, Vallergan)

2mg/kg/dose (max 60mgs) max BD(caution with use < 6 months)

Antimuscarinic effects (urinary retention, dry mouth, GI disturbance)Extrapyramidal effectsMood change, irritabilityLiver dysfunctionArrythmias

Diazepam oral and rectal RECTAL (PRN: can repeat dose x1)<1yr 2.5mg PR1-3yrs 5mg PR>3 yrs 10mg PRORAL<1yr 250micrograms/kg BD1-4 yrs 2.5mg BD5-12 yrs 5mg BD>12 yrs 10mg BD

Long half lifeDoses may be cumulativeDrowsiness, irritabilityRespiratory depressionTolerance may occur

Clomethiazole oral(Chlormethiazole)

20mg/kg/day (of edisylate) given in divided doses every 2-4 hours

Tachyphylaxis occurs quickly

Midazolam buccal (use iv preparation)

500microgram/kg (max 10mgs) sublingual

See below

Lorazepam iv Used PRN50 micrograms/kg/dose (max 4mgs)Can repeat x1 if requiredMax dose of 0.1mg/kg or 8mgs in 12 hours

Respiratory depressionHypotensionS/P Liver disease

Midazolam iv Slow iv injection of 100-200microgram/kg then infusion of 30microgram/kg/hr increasing according to response

Respiratory depressionCardiovascular depression (severe hypotension)Potentiated by erythromycin and other drugs

Clomethiazole iv(Chlormethiazole)

5-10mgs(0.6-1.25 mls of 0.8% solution)/kgs/hr. Titrate up every 2-4hrs to achieve response (max 18mgs or 2.25mls/kg/hr).Wean dose every 4-6hrs

Increased respiratory tract secretions /irritationRash, GI upsetCardiovascular depressionRespiratory depression (esp with longer infusions)Plastic giving sets must be changed every 24hrsContains high sodium content

LevodopaAll 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/dOnce total dose of levodopa is >100mgs/d switch to Sinemet-110 (10mgs carbidopa, 100mgs levodopa) as less carbidopa is preferable.

GI upsetSleep disturbanceHypotension, arrhythmiasRed urinePsychiatric manifestationsPeripheral neuropathy

Trihexyphenidyl (Benzhexol) Start 1mgs TDS (<8yrs) or 2mgs Anti-cholinergic effects

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

(urinary retention, dry mouth, dry eyes, blurred vision, Gi disturbance etc.)

Tetrabenazine <4yrs start 6.25mgs OD>4yrs start 12.5mgs OD, increasing to 12.5mgs TDSAdolescent start 25mgs OD increasing to 25mgs TDS

Onset of action can be delayed for monthsDepression which may be severe with suicidal ideation

Sulpiride If >8yrs 50mgs BD, increment total dose by 50mgs to max 100mgs BDIf <8yrs (use haloperidol in preference as doses better described) 25mgs BD, increment total dose by 25mgs to max 50mgs BD

Drowsiness at higher dosesExtrapyramidal signsTardive Kinesia

Haloperidol 12.5-25 micrograms/kg BD (max 10mg/d) further increase under guidance from Paediatric Neurologist

Extrapyramidal signsTardive 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 dystonia-induced 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 wide-

based unsteady gait, flailing movements.

Eyes: signs of dystonia of the eyes include: prolonged eyelid spasms and/or forced eye deviatons

0- Absent1- Slight: dystonia less than 10% of the time and does not interfere with tracking2- Mild: frequent blinking without prolonged spasms of eyelid closure, and/or eye

movements less than 50% of the time3- 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- Absent1- Slight: dystonia less than 10% of the time and does not interfere with speech

and/or feeding2- Mild: dystonia less than 50% of the time and does not interfere with speech and/or

feeding3- Moderate: dystonia more than 50% of the time and/or dystonia that interferes with

speech and/or feeding4- 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- Absent1- 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- Absent1- Slight: pulling less than 10% of the time and does not interfere with lying, sitting,

standing and/or walking2- Mild: pulling less than 50% of the time and does not interfere with lying, sitting,

standing and/or walking3- Moderate: pulling more than 50% of the time and/or dystonia that interferes with

lying, sitting, standing and/or walking4- 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- Absent1- Slight: dystonia less than 10% of the time and does not interfere with normal

positioning and/or functional activities2- Mild: dystonia less than 50% of the time and does not interfere with normal

positioning and/or functional activities3- Moderate: dystonia more than 50% of the time and/or dystonia that interferes with

with normal positioning and/or upper extremity function4- 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- Absent1- Slight: dystonia less than 10% of the time and does not interfere with normal

positioning and/or functional activities2- Mild: dystonia less than 50% of the time and does not interfere with normal

positioning and/or functional activities3- 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 function4- 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 compromiseo Frequent desaturationso Increased feeding support (e.g. NGT)o Recent aspiration pneumoniao Abnormal arterial gaseso Ventilatory support (supplemental oxygen / pressure support)

Metabolic disturbanceo Abnormal renal chemistryo Renal support with dialysiso Myoglobinaemia /myoglobinuriao Dehydrationo Hypoglycemia

Cardiac / Circulatory dysfunctiono Hypotensiono 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 Number of patients Medications used ? Effective drugs Comments

Jankovic and Penn, 19823

1(rhabdomyolysis, renal failure)

HaloperidolBenzhexolCarbamazepineLevodopaEthopropazineBaclofenTetrabenazineMuscle paralysis

? transient improvement with baclofen and tetrabenazine

Child later underwent bilateral thalamotomy

Marsden et al., 19844

2 patients ( 12y and 15y)

Tetrabenazine PimozideBenzhexol(1 required paralysis and ventilation)

One child responded, 1 had no response and an additional dystonic reaction with pimozide

75% of adults improved on this regimen but depression was a significant side-effect.

Vaamonde et al., 19945

1 patient

1 patient

TetrabenazinePimozideBenzhexolDiazepamBaclofenHaloperidolCarbamazepineValproatePrimidoneMuscle paralysis

ChlorpromazineHaloperidolPimozideDiazepamBenzhexolProgabideTetrabenazineBaclofenMuscle paralysis

None

Baclofen

This patient died shortly after admission

Manji et al., 19981

5 children aged 5-14yrs presenting over a 10 year period, one had rhabdomyolysis with CK 43,000 and renal failure

Chlormethiazole iv (3/5)Midazolam ivClonazepam iv/poMuscle paralysis (4/5)TetrabenazinePimozideBenzhexolValproatePrimidonePropranololDiazepamBaclofen (po/it)HaloperidolAcetazolamideBotulinum toxin

High dose benzhexol worked in one child

Acetazolamide and haloperidol worked in one child

Intrathecal baclofen and thalamotomy did not work

2/5 died, 2/5 were worse (than their pre-crisis state), 1/5 returned to his pre-crisis 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

Kyriagis et al., 20046

1 patient with Hallervorden-Spatz

BaclofenDiazepamTetrabenazineHaloperidolBenzhexol

Intrathecal baclofenPallidotomy

This patient died 15months after discharge

LevodopaBiotinMorphineIntrathecal baclofenChloral HydratePallidotomy