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 admission1. tatus dystonicus can occur in the conte!t of an acute illness affecting the central nervous system e.g. hypo!ic ischaemic "infective " metabolic encephalopathies or may occur in children with #nown chronic dystonia (either primary or secondary). $he latter group may be particularly difficult to treat and may require prolonged periods of hospitalization. Goals of treatment for children with status dystonicus: %any children presenting to the &eurology 'nit at (reat )rmond treet *ospital have dystonia. $hese guidelines are for use in those children who have severe and unremitting dystonic spasms that re uires inpatient management of associated medical complications and pain. +lear treatment goals should be established for these children before pursuing approaches that may include heavy sedation, muscle paralysis etc. (oals of treatment are usually those of achieving comfort and medical stability rather than improving function. Triggers that can e!acer"ate chronic dystonia# precipitating status dystonicus: pain from any source - (I$ esp. gastro-oesophageal reflu!, 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 $edical complications of status dystonicus: .levated body temperature /ain .!haustion from sleep deprivation and e!ertion 0habdomyolysis leading to myoglobinaemia and raised +/1 2ehydration with electrolyte disturbance from e!cess sweating 3cute renal failure as a consequence of myoglobinuria " dehydration 4ulbar dysfunction with ris# of pulmonary aspiration 0espiratory insufficiency 2eath

%N%T%&' &CT%ON: $he patients immediate medical state needs to be assessed and managed5 1. &irway compromise: 2ystonia 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 ris# of pulmonary aspiration. %any of the sedative drugs used to treat status dystonicus may compound this problem. /atients should be closely monitored for chest symptoms and signs and if present, o!ygen saturation should be monitored, a +60 performed and arterial gases measured. )ral feeding may be contra-indicated in some children and feeding via a naso-gastric or naso-7e7unal tube may be preferable. 8. (ha"domyolysis and myoglo"inaemia: %yoglobin levels (urine dipstic# positive for blood in the absence of red blood cells on urine microscopy, confirmed by plasma levels though results ta#e days) and +/1 levels (plasma) should be measured in all patients with status dystonicus and repeated 89 and 9: hours later as rise in +/1 may ta#e 89-8:hrs. ee guidelines) ;. Hydration: Increased insensible losses through sweating can rapidly lead to dehydration and maintenance fluids may need to be increased by an additional <8=> each day to compensate for increased insensible losses. .lectrolytes should be measured regularly. 9. (enal compromise: $his occurs as a consequence of dehydration and"or myoglobinuria following rhabdomyolysis. <. *ain +distress: ee# any cause of pain which may e!acerbate dystonia (see above) and treat actively. 2ystonic spasms may also be painful and appropriate analgesia (paracetamol, non-steroidal analgesics, codeine) should be given. %N%T%&' $&N&G,$,NT O*T%ONS: *harmacological -drug doses can "e o"tained here. /. Sedation and muscle rela!ation: 3 number of sedatives (triclofos or chloral and trimeprazine) and"or muscle rela!ants (oral"rectal diazepam, buccal"iv midazolam, iv lorazepam) may be useful alone or in combination to provide relief from painful and

e!hausting spasms and allow periods of sleep. .!treme care should be ta#en to monitor children when using combinations of drugs with sedating properties. 0. Heavy sedation + muscle rela!ation: $his may be required in some children for medical stability. Intravenous midazolam or chlormethiazole may be used. +hlormethiazole has the advantage that it is less of a respiratory depressant than midazolam and can be weaned to titrated oral doses. %idazolam has a long half-life, allowing slow weaning. It also has a spinal interneuron bloc#ing action, of benefit in children with dystonia. ?evels of sedation achieved with these drugs requires close monitoring of cardiovascular and respiratory function, and this may necessitate /I+' admission. 1. %ndications for paralysis and intu"ation include: 3irway compromise " respiratory failure .!haustion " severe discomfort despite ma!imal sedation and muscle rela!ants %etabolic compromise e.g. renal failure requiring haemodialysis (relative indication) Non pharmacological and supportive approaches: /. &ddressing any 2nown triggers: $here are many triggers that can underlying an episode of status dystonicus (see above). $hese should be actively sought by thorough careful history and e!amination of the child and targeted investigation. 3dequate analgesia should be provided for pain. 0. &ddress emotional + "ehavioural +psychological contri"uting factors: %any 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. $his should be considered and appropriate support provided. 1. *ositioning and handling5 /ositioning can be useful in brea#ing 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 e!acerbated by handling and this should be minimised to necessary cares. S34S,53,NT &**(O&CH: )nce the patients medical condition has been initially stabilised the following points need to be considered5 /) 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 ob7ectively assess if improvement or deterioration is occurring over time e.g. with the trial of a particular drug. +harts for documenting site and severity of dystonia using ob7ective scales8 are provided here.

0) 6hat is the li2ely aetiology of the underlying dystonia7 -N4 careful clinical and family history. +onsider the possibility of drug-induced dystonia5 &euroleptic %alignant yndrome due to antidopaminergics (including tetrabenazine, haloperidol, sulpiride), anticholinergics and also reported with sudden levodopa withdrawl. 0eported 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 par#insonism) dystonia as part of a heredodegenerative disease (e.g. Ailsons disease, 6-lin#ed dystonia-par#insonism, see investigations below) 1) 6hat targeted investigations should "e considered -depending on clinical + family history. to clarify the aetiology7
4lood5 B4+, vacuolated white cells, reticulocytes, wet blood film for acanthocytes, '@.s, ?B$s, calcium, magnesium, phosphate, uric acid, copper and ceruloplasmin, autoantibodies screen, amino acids, lactate, purines and pyramidines, lysosomal enzymes (he!osaminidase, arylsulphatase, fucosidase, C-galactosidase), acylcarnitine species, cholesterol, triglycerides, lipoprotein strip and transferrin isoelectric focussing 34+ serology (depending on clinical history) %olecular genetics (depending on clinical " family history) 5 - 2D$1 (2D$1 gene mutation in idiopathic torsion dystonia) - 2D$< mutation in dopa responsive dystonia) - /?/ +3E - 20/?3 (relevant if of Fapanese origin, or family history) - *untington (consent a significant issue, councelling required) (&45 discuss with clinical geneticist if appropriate and obtain and document parental consent in the patients notes) 'rine amino and organic acids, *G3, uric acid, copper, sulphite, oligosaccharide and mucopolysaccharide screen + B microscopy, biochemistry, lactate, amino acids, amine neurotransmitter metabolites and pterin species %uscle biopsy for histopathology, histochemistry and respiratory chain enzymes 0ectal biopsy (full thic#ness not suction) for intraneuronal storage material seen in the gangliosidoses, neuronal intranuclear inclusion disease (&I&I2) and 4attens. #in biopsy for fibroblast culture and .% of nerves 4one marrow biopsy lit-lamp e!amination (for 1-B rings) G./".0(, .&%("&+G, ..( %0I

S34S,53,NT $&N&G,$,NT O*T%ONS: Specific pharmacological therapy aimed at reducing severe dystonia -drug doses.:

$he pharmacological control of severe generalized dystonia is difficult and inpatient management is largely centred on sedation, muscle rela!ation and supportive care. +hildren with new onset dystonia in the conte!t of an acute +& illness usually improve over time and may be managed e!pectantly. +hildren with status dystonicus on a bac#ground of #nown chronic dystonia are often more difficult to manage. In such children the ris#s of complications from the severe dystonia need to be carefully measured against the ris# of side-effects from the high doses of specific anti-dystonia drugs often required. 2ecisions regarding the management of such children and use of these drugs should be made in con7unction with a +onsultant /aediatric &eurologist and patients should be closely monitored for efficacy of treatments using ob7ective dystonia scales and serial video. $he following are general guidelines for treatment options5 1. ?evodopa should be tried in all children with idiopathic primary dystonia and considered in other cases. ?evodopa trial should be continued for ; months and increased to ma!imum doses before being discontinued. 8. In children with severe and disabling dystonia, the ne!t option is a slow escalation of trihe!yphenidyl (benzhe!ol) to high dose or until side effects (anticholinergic e.g. urinary retention, blurred vision, (I 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. ;. In children in whom the above drugs have been ineffective, there is little clear evidence in previous literature to guide the ne!t approach. $etrabenazine (used at low doses because of side effect of significant depression) in combination with either sulpiride or haloperidol may be added to trihe!yphenidyl (benzhe!ol). If e!tra-pyramidal side-effects (par#insonism, a#athisia) emerge using sulpiride " haloperidol then increasing the dose of trihe!yphenidyl (benzhe!ol) may alleviate these and allow for further increases in sulpiride " haloperidol. ulpiride " haloperidol have the long term potentially irreversible side effect of tardive dys#inesia. 9. $here are case reports of a number of other drugs being useful in children with status dystonicus) <. In children with intractable severe dystonia, referral for deep brain stimulation may also be a consideration. 2r 1ate 0iney " /rof 0obert urtees " 2r +arlos de ousa 81"=<"8==9 (eferences: 1. %an7i *, *oward 0 , %iller 2* et al. tatus dystonicus5 the syndrome and its management. Brain 1HH:I181589;-8<8. 8. 4arry %F, Gan wearingen F%, 3lbright 3?. 0eliability and responsiveness of the 4arry-3lbright dystonia scale. Dev Med Child Neurol 1HHHI 915 9=9-911. ;. Fan#ovic F, /enn 3 . evere dystonia and myoglobinuria. Neurology 1H:8I;8511H<-J. 9. %arsden +2, %arion %*, Kuinn &. $he treatment of severe dystonia in children and adults. J Neurol Neurosurg Psychiatry 1H:9I9J511EE-J;.

<. Gaamonde F, &arbona F, Aeiser 0 et al. 2ystonic storms5 a practical management problem. Clin Neuropharmacol 1HH9I1J5;99-J. E. 1yriagis %, (rattan- mith /, cheinberg 3 et al. tatus dystonicus and *allervorden- patz disease5 treatment with intrathecal baclofen and pallidotomy. J Paediatr Child Health 8==9I9=5;;8-<.

(enal guidelines for the management of rha"domyolysis 2iagnosis of rhabdomyolysis is difficult5 &o relationship between severity of disease and +/1 levels %yoglobin levels rapidly rise during in7ury, then fall within E hours, +/1 is slow to rise (8-18 hrs after in7ury, pea#s 89-J8hrs later) +onsequences of rhabdomyolysis5 %yoglobinaemia (rarely measured) %yoglobinuria 5 /ositive urine dipstic# for blood, few or no red cells on microscopy, specific analysis (send to lab, ta#es days) .levated +/1 (%% band) )ther electrolyte disturbance Increased potassium Increased phosphate 2ecreased calcium Increased urate hypoglycemia with pancreatic dysfunction %anagement of rhabdomyolysis5 %a#e the diagnosis (raised +/1 (late), test urine (see above)) %anage the patient on the basis of electrolytes and not +/1. ee# advice from renal team if acute renal failure If urine output is reasonable (L =.< ml"#g"hr)5 high fluid input M ; l"m8"day (=.9<> saline"8.<> de!t) add sodium bicarbonate to fluids, aim for urine p* LJ (start with 1=mmol sodium bicarbonate " <==ml) If oligoanuric5 consider first a fluid challenge (<-1=ml"1g), possibly with frusemide to establish urine output

if unsuccessful, dialyse for severe electrolyte disturbance (+GG* should clear myoglobin reasonably well, but no real data in children) %onitor 4%s

Drug +hloral hydrate $riclofos

Doses ;=-<=mg"#g (ma! 1g"dose) tds (can be given rectally) 2ose depends on age " weight ee (uys and t $homas formulary 2) &)$ ' . AI$* +*?)03? as both derivatives of the same drug 8mg"#g"dose (ma! E=mgs) ma! 42 (caution with use N E months)

Side ,ffects to loo2 for (astric irritant, 0ash, *eadache 1etonuria .osinophilia, low A++ 2erivative of chloral hydrate. ame side effects but less gastric irritation 3ntimuscarinic effects (urinary retention, dry mouth, (I disturbance) .!trapyramidal effects %ood change, irritability ?iver dysfunction 3rrythmias ?ong half life 2oses may be cumulative 2rowsiness, irritability 0espiratory depression $olerance may occur

3limemazine ($rimeprazine, Gallergan)

2iazepam oral and rectal

+lomethiazole oral (+hlormethiazole) %idazolam buccal (use iv preparation) ?orazepam iv

%idazolam iv

0.+$3? (/0&5 can repeat dose !1) N1yr 8.<mg /0 1-;yrs <mg /0 L; yrs 1=mg /0 )03? N1yr 8<=micrograms"#g 42 1-9 yrs 8.<mg 42 <-18 yrs <mg 42 L18 yrs 1=mg 42 8=mg"#g"day (of edisylate) given in divided doses every 8-9 hours <==microgram"#g (ma! 1=mgs) sublingual 'sed /0& <= micrograms"#g"dose (ma! 9mgs) +an repeat !1 if required %a! dose of =.1mg"#g or :mgs in 18 hours low iv in7ection of 1==8==microgram"#g then infusion of ;=microgram"#g"hr increasing according to response <-1=mgs(=.E-1.8< mls of =.:> solution)"#gs"hr. $itrate up every 89hrs to achieve response (ma! 1:mgs or 8.8<mls"#g"hr). Aean dose every 9-Ehrs

$achyphyla!is occurs quic#ly ee below 0espiratory depression *ypotension "/ ?iver disease 0espiratory depression +ardiovascular depression (severe hypotension) /otentiated by erythromycin and other drugs Increased respiratory tract secretions "irritation 0ash, (I upset +ardiovascular depression 0espiratory depression (esp with longer infusions)

+lomethiazole iv (+hlormethiazole)

?evodopa 3ll doses quoted are for the levodopa component of Sinemet

$rihe!yphenidyl (4enzhe!ol)

$etrabenazine

ulpiride

*aloperidol

Sinemet-6 .! (carbidopa 18.<mg, levodopa <=mgs)5 start 1mg"#g"d (unless N1yr5 =.8<mg"#g"d) increasing to ma! dose 1=mg"#g"d )nce total dose of levodopa is L1==mgs"d switch to Sinemet-""# (1=mgs carbidopa, 1==mgs levodopa) as less carbidopa is preferable. tart 1mgs $2 (N:yrs) or 8mgs $2 (L:yrs). Increase total dose by 1mg (N:yrs) or 8mgs (L:yrs) every J days until clinical effect or side effects intervene or ma! dose 1=mgs $2 N9yrs start E.8<mgs )2 L9yrs start 18.<mgs )2, increasing to 18.<mgs $2 3dolescent start 8<mgs )2 increasing to 8<mgs $2 If L:yrs <=mgs 42, increment total dose by <=mgs to ma! 1==mgs 42 If N:yrs (use haloperidol in preference as doses better described) 8<mgs 42, increment total dose by 8<mgs to ma! <=mgs 42 18.<-8< micrograms"#g 42 (ma! 1=mg"d) further increase under guidance from /aediatric &eurologist

/lastic giving sets must be changed every 89hrs +ontains high sodium content (I upset leep disturbance *ypotension, arrhythmias 0ed urine /sychiatric manifestations /eripheral neuropathy 3nti-cholinergic effects (urinary retention, dry mouth, dry eyes, blurred vision, (i disturbance etc.) )nset of action can be delayed for months 2epression which may be severe with suicidal ideation 2rowsiness at higher doses .!trapyramidal signs $ardive 1inesia

.!trapyramidal signs $ardive 1inesia

4arry8&l"right Dystonia Scale

(4arry %F, Gan wearingen F%, 3lbright 3?. 0eliability and responsiveness of the 4arry-3lbright dystonia scale. Dev Med Child Neurol 1HHHI 915 9=9-911)

$his scale produces a reliable total score for children with generalized dystonia, but reliability of scores of individual regions is less. $o enhance reliability in scores with repeated measures, this scale should preferably be used by someone with e!perience 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)

*atients Name: Date of &ssessment:

Hospital Num"er:

%f this is a repeat assessment# please indicate the reason for reassessment: &ssessor: &ssessors position -medical# physio# OT.: 9ideo ta2en with parental consent: : + N %f yes# location where video stored for future reference: 2irections5 3ssess the patient for dystonia in each of the following regions5 eyes, mouth, nec#, trun#, each upper and lower e!tremity (: body regions). Arite the scores on the lines provided. 0ate severity based only on dystonia as evidenced by abnormal movements or postures. Ahen assessing functional limitations, do not score as dystoniainduced functional limitation if other factors, such as wea#ness, lac# of motor control,

cognitive deficits, persistent primitive refle!es, and"or other movement disorders are contributing to functional limitation. 2efinitions of movement disorders5 - 2ystonia5 sustained muscle contractions caused by twisting and repetitive movements or abnormal postures pasticity5 Gelocity-dependent resistance to passive movement - 3thetosis5 2istal writhing or contorting movements - +horea5 4rief, rapid, unsustained, irregular movements - 3ta!ia5 Incoordination of movement characterized by widebased unsteady gait, flailing movements. ,yes: signs of dystonia of the eyes include5 prolonged eyelid spasms and"or forced eye deviatons =- 3bsent 1- light5 dystonia less than 1=> of the time and does not interfere with trac#ing 8- %ild5 frequent blin#ing without prolonged spasms of eyelid closure, and"or eye movements less than <=> of the time ;- %oderate5 prolonged spasms of eyelid closure, but eyes open most of the time, and"or eye movements more than <=> of the time that interfere with trac#ing, but able to resume trac#ing 9- evere5 /rolonged spasms of eyelid closure, with eyelids closed at least ;=> of the time, and"or eye movements more than <=> of the time that prevent trac#ing O- 'nable to assess eye movements ( uggest video eyes and upper face (at rest and with eyes open and closed if possible) for minimum of 8 minutes followed by period of video of the patient visually fi!ing on and then trac#ing an ob7ect " face) ,yes scored ;;;;;; $outh: signs of dystonia of the mouth include grimacing, clenched or deviated 7aw, forced open mouth, and"or forceful tongue thrusting =- 3bsent 1- light5 dystonia less than 1=> of the time and does not interfere with speech and"or feeding 8- %ild5 dystonia less than <=> of the time and does not interfere with speech and"or feeding ;- %oderate5 dystonia more than <=> of the time and"or dystonia that interferes with speech and"or feeding 9- evere5 dystonia more than <=> of the time and"or dystonia that prevents speech and"or feeding O- 'nable to assess mouth movements

( uggest video of mouth for minimum of 8 minutes followed by period of speech (reading, conversation and sounds tee, mee, la, #a and prolonged holding of eeeeeee), tongue protrusion and feeding solids"liquids if safe) $outh scored;;;;;; Nec2: signs of dystonia of the nec# include pulling of the nec# into any plane of motion5 e!tension, fle!ion, lateral fle!ion or rotation =- 3bsent 1- light5 pulling less than 1=> of the time and does not interfere with lying, sitting, standing and"or wal#ing 8- %ild5 pulling less than <=> of the time and does not interfere with lying, sitting, standing and"or wal#ing ;- %oderate5 pulling more than <=> of the time and"or dystonia that interferes with lying, sitting, standing and"or wal#ing 9- evere5 pulling more than <=> of the time and dystonia that prevents sitting in a standard wheelchair (e.g. requires special head rest), standing and"or wal#ing O- 'nable to assess nec# movements ( uggest 3/ and lateral video of nec# at rest with head unsupported for minimum of 8 minutes each view, then if possible as# to move nec# in all planes and to sit, stand, wal#) Nec2 scored;;;;;; Trun2: signs of dystonia of the trun# include pulling of the trun# into any plane of motion5 e!tension, fle!ion, lateral fle!ion or rotation =- 3bsent 1- light5 pulling less than 1=> of the time and does not interfere with lying, sitting, standing and"or wal#ing 8- %ild5 pulling less than <=> of the time and does not interfere with lying, sitting, standing and"or wal#ing ;- %oderate5 pulling more than <=> of the time and"or dystonia that interferes with lying, sitting, standing and"or wal#ing 9- evere5 pulling more than <=> of the time and dystonia that prevents sitting in a standard wheelchair (e.g. requires adapted seating system), standing and"or wal#ing O- 'nable to assess trun# movements ( uggest 3/ and lateral video at rest with trun# unsupported for minimum of 8 minutes each view, then if possible as# to move trun# in all planes and to sit, stand, wal#) Trun2 scored;;;;;;

3pper e!tremities: signs of dystonia of the upper e!tremities include sustained muscle contractions causing abnormal postures =- 3bsent 1- light5 dystonia less than 1=> of the time and does not interfere with normal positioning and"or functional activities 8- %ild5 dystonia less than <=> of the time and does not interfere with normal positioning and"or functional activities ;- %oderate5 dystonia more than <=> of the time and"or dystonia that interferes with with normal positioning and"or upper e!tremity function 9- evere5 dystonia more than <=> of the time and"or dystonia that prevents normal positioning and"or upper e!tremity function (e.g. arms restrained to prevent in7ury) O- 'nable to assess upper e!tremity movements ( uggest video of each upper limb at rest for minimum ;= seconds followed by video of positoning (ability to sustainP) and attempt at basic functional activity e.g. holding ob7ect, releasing ob7ect, touching ob7ect, drawing) 'eft upper lim" scored;;;;;;;; (ight upper lim" scored;;;;;;; 'ower e!tremities: signs of dystonia of the upper e!tremities include sustained muscle contractions causing abnormal postures =- 3bsent 1- light5 dystonia less than 1=> of the time and does not interfere with normal positioning and"or functional activities 8- %ild5 dystonia less than <=> of the time and does not interfere with normal positioning and"or functional activities ;- %oderate5 dystonia more than <=> of the time and"or dystonia that interferes with with normal positioning and"or lower e!tremity weight bearing and"or function 9- evere5 dystonia more than <=> of the time and"or dystonia that prevents normal positioning and"or lower e!tremity weight bearing and"or function O- 'nable to assess lower e!tremity movements ( uggest video of each lower limb at rest for minimum ;= seconds followed by video of positoning (ability to sustainP) and attempt at basic functional activity e.g. sitting, standing (front, bac# and lateral view), wal#ing towards and away, tapping floor with ball and heel of foot) 'eft lower lim" scored;;;;;;;; (ight lower lim" scored;;;;;;; TOT&' SCO(, ;;;;;;;;;

ite (please circle which is most suitable for patient at time of scoring)5 segmental dystonia - two or more ad7acent focal areas, usually head and nec#, trun# 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

/lease document level of pain and distress at time of scoring (from standardized pain assessment charts)5 &one, %ild, %oderate, evere. /lease document medication and doses at time of scoring5

%edical $eam to document relevant information re medical status which may affect scoring (please tic#)5 0espiratory " 4ulbar compromise o Brequent desaturations o Increased feeding support (e.g. &($) o 0ecent aspiration pneumonia o 3bnormal arterial gases o Gentilatory support (supplemental o!ygen " pressure support) %etabolic disturbance o 3bnormal renal chemistry o 0enal support with dialysis o %yoglobinaemia "myoglobinuria o 2ehydration o *ypoglycemia +ardiac " +irculatory dysfunction o *ypotension o 3bnormal heart rate " rhythm )ther

If side-effects have been e!perienced 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 case5

(eview of previous literature reports of management of status dystonicus:

3uthors Fan#ovic and /enn, 1H:8; &umber of patients 1 (rhabdomyolysis, renal failure) %edications used *aloperidol 4enzhe!ol +arbamazepine ?evodopa .thopropazine 4aclofen $etrabenazine %uscle paralysis $etrabenazine /imozide 4enzhe!ol (1 required paralysis and ventilation) $etrabenazine /imozide 4enzhe!ol 2iazepam 4aclofen *aloperidol +arbamazepine Galproate /rimidone %uscle paralysis +hlorpromazine *aloperidol /imozide 2iazepam 4enzhe!ol /rogabide $etrabenazine 4aclofen %uscle paralysis +hlormethiazole iv (;"<) %idazolam iv P .ffective drugs P transient improvement with baclofen and tetrabenazine +omments +hild later underwent bilateral thalamotomy

%arsden et al., 1H:99

8 patients ( 18y and 1<y)

Gaamonde et al., 1HH9<

1 patient

)ne child responded, 1 had no response and an additional dystonic reaction with pimozide &one

J<> of adults improved on this regimen but depression was a significant side-effect. $his patient died shortly after admission

1 patient

4aclofen

%an7i et al., 1HH:1

< children aged <-19yrs presenting over a 1=

*igh dose benzhe!ol

8"< died, 8"< were worse (than their pre-

year period, one had rhabdomyolysis with +1 9;,=== and renal failure

+lonazepam iv"po %uscle paralysis (9"<) $etrabenazine /imozide 4enzhe!ol Galproate /rimidone /ropranolol 2iazepam 4aclofen (po"it) *aloperidol 3cetazolamide 4otulinum to!in 4aclofen 2iazepam $etrabenazine *aloperidol 4enzhe!ol ?evodopa 4iotin %orphine Intrathecal baclofen +hloral *ydrate /allidotomy

wor#ed in one child 3cetazolamide and haloperidol wor#ed in one child Intrathecal baclofen and thalamotomy did not wor# Intrathecal baclofen /allidotomy

crisis state), 1"< returned to his pre-crisis state. 3ll had prolonged admissions everal triggers for e!acerbating dystonia identified in these children /imozide was associated with significant cardiac to!icity in 8"< children $his patient died 1<months after discharge

1yriagis et al., 8==9E

1 patient with *allervorden- patz