Dystonic storm: a practical clinical and video review

Dystonic storm usually occurs in patients who are already known to have dystonia, and are usually followed in movement disorders clinic. De novo presentation of a patient in dystonic storm is rare. Mean prior dystonia duration is 6 years, with an average age at presentation of 14 years [6]. Dystonic storm tends to occur in patients with severe or poorly controlled dystonia at baseline [2, 9], and one-third of events are unprovoked [6, 10]. Among provoked events, triggers include infection (50%) and medication change (30%). Examples of the latter include ITB withdrawal [11, 12], reduction or withdrawal of other dystonia medications or initiation of D-penicillamine in Wilson’s disease [13, 14]. Other examples include introduction of clonazepam (paradoxically it can also be used as treatment of dystonic storm) [1], initiation of zinc in Wilson’s disease [15] or zolpidem discontinuation in Parkinson’s disease [16]. Other provoking factors include surgical procedures and deep brain stimulation (DBS) failure [17, 18]. As DBS has become more widespread, there have been more reports of dystonic storm from DBS failure, especially due to battery issues or at the end of battery life [19].

In some patients a prodrome of dystonic storm may occur, where dystonia is worsened from baseline but not as severe as in true storm (Fig. 2 and Additional file 2: Video segment 2). Once true storm begins, it usually lasts 2–4 weeks with gradual recovery. However even with treatment, mortality remains 10% [6]. If the patient survives, they may return back to their baseline severity of dystonia (full recovery) or be left with some residual deficits (partial recovery) [6]. Relapses are common, and patients with a history of one event should be monitored for recurrence.

Once dystonic storm has begun, management must be initiated promptly. Hospital admission is generally required and patients should be admitted to the intensive care unit. The strategy of management differs in the acute and subacute periods. Here we divide the management into the first 24 h (Fig. 3a and b) vs. the next 2–4 weeks (Table 4). This distinction reflects the critical nature of the decisions that must be made within the first 24 h in order to minimize morbidity and mortality.

DYSTONIA SPECIFIC Rxa	SUPPORTIVE Rx
Anticholinergics	1st line: IV midazolam
DA receptor blockersb	2nd line: Propofol
TBZ	3rd line: Non-depolarizing neuromuscular blockers or Barbiturates
Clonidine
Baclofen + Assorted drugs

^aCombination is typically required

^bShould be avoided when dystonic storm developing from underlying tardive dystonia

This table demonstrates the list of dystonia-specific and supportive therapies. Dystonia-specific medications alone are often ineffective in isolation to control dystonic storm. Combinations of drugs are generally required. Intravenous midazolam is typically employed as a first-line agent, whereas propofol is second-line. In refractory cases, third-line agents include non-depolarizing neuromuscular blocking agents (such as pancuronium) or barbiturates

Abbreviations: DA dopamine, IV intravenous, Rx treatment, TBZ tetrabenazine

The main aims of management during the first 24 h are 1) to identify triggers and their specific treatments and 2) to assess whether or not the patient is a candidate for globus pallidus interna (GPi) DBS or ITB therapy. Some may argue that invasive therapies such as GPi DBS or ITB should be considered as last resort treatments, to be used when dystonic storm is refractory to other therapies [23]. Nevertheless, with increased utilization of DBS in the past decade, the pendulum may be shifting away from this approach. An increasing number of reports have demonstrated excellent outcomes of GPi DBS and ITB in dystonic storm [10, 21, 24–37], especially in DYT1 generalized dystonia and other primary dystonia cases (Additional file 4: Video segment 4). Due to the dramatic impact on patient outcome, the modern trend is to advocate a tiered approach (based on diagnosis e.g. generalized DYT1 dystonia and severity) [5, 38] with consideration of GPi DBS or ITB therapy [21, 26–29, 39]. Patients in dystonic storm often improve immediately with DBS [8, 24], as opposed to the delayed benefit (weeks to months) of DBS in other forms of dystonia. ITB use may be limited by its complications, especially hardware failure and infection [37]. Pallidotomy [31, 40–42] is rarely used unless DBS is unavailable.

Another important question when approaching a critically ill hyperkinetic patient is to distinguish dystonic and choreic storm from other movement disorder emergencies, as delineated in Table 1 (Additional file 5: Video segment 5). Predisposing conditions in both pure dystonic storm and mixed dystonic/choreic storm are often similar, for example in the clinical scenarios of CP, traumatic brain injury and Leigh’s syndrome. Patients with dystonic storm may also have co-existing chorea. While dystonic and choreic storms appear similar, the management of choreic storm should focus on identifying and treating the underlying trigger. Nonketotic hyperglycemia, biballism, lupus, severe Sydenham’s chorea, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and CP with exacerbation can cause choreic storm. The treatment of dystonic and choreic storms overlaps somewhat: neuroleptics, tetrabenazine and GPi DBS [24], with the exception of anticholinergics (which can worsen chorea). Nevertheless, the therapeutic strategy for pure dystonic or mixed dystonic/choreic storm should follow the dystonic storm paradigm discussed below (Fig. 3).

A proposed flow chart for dystonic storm management in the first 24 h is demonstrated in Fig. 3b. Triggers such as infection or medication change should be identified and treated accordingly, for example by initiating antibiotics or restoring prior medications such as dopamine receptor blockers, ITB, clonazepam or trihexyphenidyl. If the patient is known or likely to have DYT1 generalized dystonia, immediate neurosurgical consultation should be obtained to consider emergent bilateral GPi DBS. We would also suggest this approach for patients with DYT1-negative primary dystonia.

If the patient does not meet these criteria, effective communication with the patient’s family is essential. The efficacy of medical management of dystonic storm is only 10% [6] and mortality remains about 10% [6]. Primary questions to be answered are 1) What are the family’s goals of care? and 2) Is the patient a neurosurgical candidate for ITB or GPi DBS (or ablative surgery) should medical therapies fail? If the patient is not a surgical candidate, management remains medical. Table 4 demonstrates the list of usual medical treatments employed over the next 2–4 weeks. These can be separated into dystonia specific therapies and supportive treatment. Dystonia specific treatment includes anticholinergics, dopamine receptor blockers, tetrabenazine, clonidine, baclofen and assorted drugs. The so-called “Marsden cocktail”, a combination of tetrabenazine 75 mg/day, pimozide and benzhexol, was first employed in England [3]. Management remains empiric, without evidence-based guideline. Regardless of the combinations, the key is to use multiple high-dose anti-dystonic agents to control or abort storm, rather than slowly titrating one agent at a time. Of note, dopamine receptor blockers should be avoided in dystonic storm developing from underlying tardive dystonia.

Along with dystonia-specific treatment, supportive measures include airway protection, sedation and pain control. Dystonia-specific therapies alone are often ineffective, or may require days to weeks before achieving improvement. Anesthetic agents typically used in dystonic storm include intravenous midazolam, propofol, and barbiturates. Intravenous midazolam is generally selected as a first choice due to its muscle relaxation effect, short half-life, rapid onset of action, and good cardiovascular profile [1, 9, 43]. If the symptoms are not controlled, propofol, an anesthetic with relatively short half-life, is generally considered as a second line agent. Third line drugs are non-depolarizing paralytic agents such as pancuronium and barbiturates. Of note, depolarizing neuromuscular blocking agents such as suxamethonium should be avoided due to their potential risk of rhabdomyolysis.

Dystonic storm is rare and evidence-based guidelines for management are lacking. The true incidence and prevalence of dystonic storm remains unclear. Evidence-based guidelines addressing medication selection, drug order, timing, dose, polypharmacy, the role of intravenous sedation and intubation, as well as the timing and patient selection criteria for DBS and ITB are desperately needed. In addition, early consideration of DBS remains a challenging issue in some countries where this treatment modality is not available.