DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY GUIDELINE Status dystonicus: a practice guide NICHOLAS M ALLEN1 | JEAN-PIERRE LIN2 | TIM LYNCH3 | MARY D KING1 1 Department of Paediatric Neurology and Clinical Neurophysiology, Children’s University Hospital, Dublin, Ireland. 2 General Neurology & Complex Motor Disorders Service, Evelina Children’s Hospital, Guy’s & St Thomas’ NHS Foundation Trust, London, UK. 3 Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland. Correspondence to Dr Nicholas M Allen, Department of Paediatric Neurology, Children’s University Hospital, Temple Street, Dublin 1, Ireland. E-mail: [email protected] Status dystonicus is a rare, but life-threatening movement disorder emergency. Urgent PUBLICATION DATA assessment is required and management is tailored to patient characteristics and complica- Accepted for publication 7th October 2013. tions. The use of dystonia action plans and early recognition of worsening dystonia may Published online 4th December 2013 potentially facilitate intervention or prevent progression to status dystonicus. However, for established status dystonicus, rapidly deployed temporizing measures and different depths of ABBREVIATIONS sedation in an intensive care unit or high dependency unit are the most immediate and effec- DBS Deep brain stimulation tive modalities for abating life-threatening spasms, while dystonia-specific treatment takes ITB Intrathecal baclofen effect. If refractory status dystonicus persists despite orally active anti-dystonia drugs and unsuccessful weaning from sedative or anaesthetic agents, early consideration of intrathecal baclofen or deep brain stimulation is required. During status dystonicus, precise documenta- tion of dystonia sites and severity as well as the baseline clinical state, using rating scales and videos is recommended. Further published descriptions of the clinical nature, timing of evolution, resolution, and epidemiology of status dystonicus are essential for a better collective understanding of this poorly understood heterogeneous emergency. In this review, we provide an overview of the clinical presentation and suggest a management approach for status dystonicus. UNDERSTANDING AND DIAGNOSING STATUS children,4 and CP is the most common cause. This review DYSTONICUS focuses on the most acute life-threatening complication of Dystonia: phenomenology and classification dystonia, status dystonicus. Dystonia, traditionally classified as a hyperkinetic movement disorder, manifests in a variety of ways. It is characterized by Status dystonicus involuntary sustained or intermittent muscle contractions Status dystonicus, also known as dystonic storm or dystonic causing repetitive twisting movements, abnormal postures, crisis, is a life-threatening movement disorder emergency. or both.1 A characteristic feature of dystonia is the presence Although considered rare (only about 100 published cases), of muscle co-contraction, exacerbation with the intention to status dystonicus is most likely an underreported condition, move and/or non-specific afferent stimuli, and complete res- heterogeneous in its aetiology, pathogenesis, presentation, olution of dystonia by sleep, irrespective of the mechanism course, and outcome. Status dystonicus affects all age groups of dystonia. This last observation distinguishes dystonia but up to 60% of patients are between ages 5 years and from lower brainstem, spinal, and intramuscular hyper-acti- 16 years, although patients may be younger or older, with a vation states. Dystonia distorts voluntary movements and male preponderance.5 Neurometabolic disorders such as often coexists with other movement and motor disorders glutaric aciduria type 1 may precipitate status dystonicus as such as choreoathetosis in dyskinetic cerebral palsy (CP), early as 7 months of age and the extensor dystonia is often myoclonus, or parkinsonism. Dystonic postures may give the mistaken for status epilepticus. impression of hypokinesia.1,2 Topographically, dystonia may affect a single body site (focal dystonia), several body sites, or Phenomenology and diagnosis be classified as generalized (involving both legs and one or Status dystonicus is characterized by the development of more body region such as axial muscles). Until recently,3 increasingly frequent or continuous severe episodes of dystonia was usually classified in terms of whether it generalized dystonic spasms (contractions) and requires occurred as part of a primary dystonia disorder, a dystonia- urgent (hospital) management.6,7 Recent phenomenological plus syndrome, a paroxysmal dyskinesia (dystonia), a hered- categorization divides episodes of status dystonicus into either odegenerative disorder, or secondary dystonia (acquired tonic (mainly sustained contractions and abnormal postures) or secondary to a symptomatic cerebral, brainstem, or spinal phasic (rapid and repetitive dystonic contractions) phenotypes. cord insult). Secondary dystonia is more common in The tonic phenotype is more common in males and in © 2013 Mac Keith Press DOI: 10.1111/dmcn.12339 105 secondary (acquired) dystonias, and has a potentially worse What this paper adds 5 outcome. The movements of status dystonicus may also • An overview of status dystonicus and a practical approach to the manage- overlap with additional, sometimes prominent, hyperkinesias ment of status dystonicus and ‘pre-status dystonicus’. such as choreoathetosis, which can make objective recogni- tion complicated.6,8,9 Currently, there is no internationally Medications reported to trigger status dystonicus are agreed definition for status dystonicus. Criteria, including important, particularly the dopamine-receptor blockers 16 life-threatening complications proposed by Manji et al. are pimozide (exacerbated status dystonicus) and haloperidol 17 often cited.6 All patients in that case series developed one or as both can be used to treat dystonia and chorea. Metoclo- 8 more of the following: (1) bulbar weakness compromising pramide can have the same effect. Clonazepam has been airway patency, (2) progressive impairment of respiratory reported as a trigger (possibly coincidental) of status dysto- 6,18,19 function leading to respiratory failure, (3) metabolic nicus. In Wilson disease the introduction of chelation 20,21 7 22 derangements, and (4) exhaustion and pain. therapy with penicillamine, zinc sulphate, or trientine In practice, status dystonicus often occurs at the end of have also been implicated in status dystonicus. Clozapine 19 a continuum of worsening dystonia. Along such a contin- treatment has been implicated, as well as withdrawal of 6 uum, a recently described simplified dystonia severity lithium and tetrabenazine. Deep brain stimulation failure 5,8 action plan may be useful to assess children at risk of sta- caused by hardware problems, intrathecal baclofen pump 12 tus dystonicus and decide on the level of care required failure, as well as routine baclofen, and benzodiazepine for management (see Fig. 1 and the supplementary mate- withdrawal in general should be considered where relevant. rial of Lumsden et al. for related clinical vignettes employed to validate the scale).10 In addition, the sites Complications and related investigations and severity of the dystonia may be documented using The muscle spasms or dystonic movements during status dystonia rating scales such as the Dyskinesia Impairment dystonicus give rise to complications that are at best painful 5 Scale for patients with cerebral palsy2 or the Burke- and uncomfortable, and at worst life-threatening. Severe Fahn-Marsden rating scale.11 Video recordings are generalized muscle spasms may cause respiratory compro- important for diagnosis and follow-up of treatment mise and severe metabolic disturbances, particularly rhabd- response. The baseline neurological state (coexisting omyolysis and acute renal failure. The initial investigations spasticity, etc.) should also be recorded. are based on consideration of the complications, need for monitoring, supportive measures, and likely trigger factors. Aetiology Respiratory failure can be a function of dystonic bulbar Status dystonicus usually emerges gradually after weeks or spasms (pharyngeal, laryngeal), truncal-respiratory muscle months in the patient with an underlying dystonia diagnosis. spasm, diaphragm dystonia, generalized exhaustion, aspira- However, status dystonicus may also present during new tion pneumonia, and indeed the need for highly sedative onset dystonic disorders without previous or only mild and relaxant cocktails of drugs used to control status dysto- dystonic movements.5,10,12,13 Some patients are prone to nicus. Relevant respiratory investigations for these compli- recurrent episodes. The acquired dystonias are the most cations and triggers include chest X-ray, pulse oximetry, common underlying dystonias leading to status dystonicus and blood gas monitoring, all of which should be part of (38% of cases), CP being the most common individual sec- the initial and ongoing supportive measures. ondary cause followed by the previously termed ‘heredode- The biochemical derangements resulting from significant 23 generative dystonias’ (particularly neurodegeneration with rhabdomyolysis include elevated creatine kinase (usually > > brain iron accumulation, Wilson disease, and mitochondrial 5 times normal range, e.g. 1000 IU/L), myoglobinaemia, disorders) and the ‘pure primary dystonias’.5 However, any myoglobinuria, electrolyte abnormalities,