Reminder of important clinical lesson

CASE REPORT

Medication-induced acute dystonic reaction:
the challenge of diagnosing movement disorders
in the intensive care unit
Geneviève Digby, Shirin Jalini, Sean Taylor
Queen’s University, Kingston,
Ontario, Canada
Correspondence to
Dr Geneviève Digby,
genevieve.digby@gmail.com
Accepted 5 September 2015

SUMMARY
A 62-year-old man presented with left middle cerebral
artery stroke. 1 h postadministration of tissue
plasminogen activator, he received a total of 4 mg of
haloperidol for combativeness. He developed partial
complex status epilepticus, requiring benzodiazepines,
phenytoin, propofol and intubation. 5 h later, he
developed recurrent stereotyped tonic movements
involving arching of the back, extension of the arms and
contraction of opposing muscle groups. Repeat CT scan
of the head showed evolving insular infarct. Differential
diagnoses for these movements included tonic/clonic
seizures, extensor (decerebrate) posturing from
haemorrhagic conversion, neuroleptic malignant
syndrome, or dystonic reaction. Given the lack of
response to antiseizure medications, the recent
administration of haloperidol, and the prompt resolution
of movements following diphenhydramine administration,
an acute dystonic reaction was considered. This atypical
case of a critically ill patient with stroke highlights the
fact that these patients may have multiple abnormal
movements requiring careful analysis to guide diagnosisspecific management.

BACKGROUND

To cite: Digby G, Jalini S,
Taylor S. BMJ Case Rep
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Movement disorders in critically ill neurological
patients are common, though diagnosis may be
complicated by patients’ critical state, complex
monitoring and polypharmacy. In fact, the differential diagnosis for abnormal movements in these
patients is broad and careful evaluation of the semiology of movements, as well as potential causative
factors, may assist with proper diagnosis and
correct treatment. Patients with acute stroke are at
increased risk of seizures, which occur in 4–10%,1
as well as delirium, which occurs in 13–48%.2
Medications such as antipsychotics are often used
to manage delirium and may lead to extrapyramidal
side effects in up to 4.5% of patients.3 The management of movement disorders varies depending
on the aetiology; antiepileptics such as benzodiazepines are the cornerstone of acute seizure management, while anticholinergics and withdrawal of
offending agents are the management for dystonic
reactions. Additionally, focal neurological deficits
due to stroke can further complicate the analysis of
abnormal movements, thereby delaying diagnosis
and appropriate management.
We present an atypical case of a patient with
acute stroke who exhibited three separate patterns
of movement: focal neurological deficits, clonic

movements suspicious for partial seizure and a
drug-induced acute dystonic reaction. This case will
highlight the importance of careful evaluation of
the semiology of movements to permit proper diagnosis and will discuss treatment-related issues that
can minimise the risk of dystonic reactions in critically ill patients.

CASE PRESENTATION
A 62-year-old right-handed man presented with
recurrent left middle cerebral artery (MCA) syndrome (National Institutes of Health Stroke Scale
(NIHSS) 14) on a background of restless legs syndrome treated with pramipexole 0.5 mg nightly for
the preceding 2 years. One-hour post-thrombolysis,
he became agitated and received 1 mg of haloperidol. He continued to be very combative and was
administered 5 mg of lorazepam, but continued to
display dangerous behaviours. Over the following
half hour, he received an additional 3 mg of haloperidol to attempt to control his agitated state.
Minutes later, he developed suspected partial
complex status epilepticus manifesting as clonic
activity of the right arm and hand; this did not
respond to an additional 4 mg of lorazepam and
6.5 mg of midazolam. The patient developed a
reduced level of consciousness and was therefore
intubated with propofol 320 mg as an anaesthetic,
and administered 1.5 g of phenytoin, which led to
resolution of the suspected seizure activity. Repeat
imaging showed appropriate evolution of left parietal and insular ischaemia. Five hours later, the
patient developed back arching and recurrent bilateral leg extensor muscle contraction (video 1). Each
episode lasted less than 10 s and occurred 2–3
times per minute. There were no versive head or
eye movements and no clonic activity was noted.
Repeat CT scan of the head was unchanged. The
movements persisted, despite an infusion of 8 mg/h
of midazolam, but stopped abruptly following
administration of intravenous diphenhydramine.

INVESTIGATIONS
In light of the evolution of three separate movement disorders, this patient underwent three CT
scans of the head on the day of presentation: the
first to confirm ischaemic stroke (figure 1), and the
second and third to rule out haemorrhagic transformation after development of status epilepticus,
followed by the movements seen in the video 1,
which were later recognised to be an acute dystonic
reaction. The repeat CT scans only revealed

Digby G, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-207215

1

Reminder of important clinical lesson
L, and, while elevated, could have been attributed to the
patient’s prior agitation. Finally, in light of recent administration
of haloperidol and resolution with diphenhydramine, an acute
dystonic reaction (involuntary, sustained, repetitive opposing
muscle contractions8) was considered.

TREATMENT

Video 1 Acute dystonic reaction causing recurrent whole body
extensor posturing. Episodes such as these would last several seconds
and recur up to 2–3 times per minute.
evolving ischaemic stroke with no evidence of haemorrhagic
transformation.
While EEG would have been useful to help rule out seizures
as the cause of the abnormal movements, and may have led to a
more rapid diagnosis, our centre does not have 24 h EEG capabilities and these episodes occurred exclusively at night. As
such, examining the semiology of movement was of utmost
importance and a trial of treatment for the leading differential
diagnosis was required. EEG was, however, performed the
following day once the dystonic reaction and seizures had been
treated, and revealed no epileptiform activity, with slight slow
activity in the left frontotemporal region due to left MCA
stroke.

In order to treat the suspected acute dystonic reaction, the
patient received 50 mg of diphenhydramine and the abnormal
movements quickly resolved. Two days later, the patient exhibited extreme agitation not responsive to benzodiazepines and
was therefore started on quetiapine 50 mg every 6 h, a frequently administered medication in the intensive care unit (ICU)
due to its ability to reduce duration of delirium and agitation
without significantly affecting respiratory status.9 Another
2 days later, metoclopramide 50 mg every 6 h was initiated
according to local ICU protocol for poor gastric absorption of
feeds, given its prokinetic effects, while its central antidopaminergic actions and risk of associated dystonic reactions were not
considered at the time.9 Over the course of the following day,
the abnormal movements demonstrated in video 1 reappeared,
but this time they were more quickly identified and were less
severe. A total of 100 mg of diphenhydramine was administered,
but movements did not completely resolve until 1 mg of benzatropine was administered. This functioned as an unintended
rechallenge with an antipsychotic for a patient who, prior to
admission, had been antipsychotic naïve; the recurrence of dystonic movements confirmed that the patient was prone to
develop an acute dystonic reaction with exposure to these medications. As such, all antipsychotics and antidopaminergics were
withdrawn and no further dystonic reactions occurred. The
patient continued on pramipexole for restless legs throughout
the admission and after discharge.

DIFFERENTIAL DIAGNOSIS
The differential diagnosis for this patient’s abnormal movements
is broad. Considerations included tonic seizure (asymmetrical,
sudden extension/flexion of extremities4), which occur in
4–10% of patients poststroke, with most occurring within the
first 48 h.1 The high NIHSS and cortical involvement in this
patient further increased the risk,5 as did the administration of
neuroleptics, which can reduce seizure threshold.6 However,
seizure was thought to be less likely as the movements occurred
despite the fact that the patient was receiving benzodiazepines,
propofol and phenytoin. Extensor (decerebrate) posturing (arm
adduction and extension, wrist pronation and back arching7)
secondary to haemorrhagic conversion was considered, but
thought to be less likely due to the symmetric presentation of
movements and unchanged imaging. Neuroleptic malignant syndrome was thought to be less likely given that the patient was
afebrile and not rigid between episodes. A creatine kinase level
checked a few hours after the movements occurred was 824 U/

Figure 1 CT scan of the head. (A) Embolus in distal left M3 just
superior to insula, and (B) and (C) Alberta Stroke Programe Early CT
Score (ASPECTS) 10.
2

OUTCOME AND FOLLOW-UP
The patient’s course in the ICU was prolonged and complicated
by vocal cord dysfunction requiring re-intubation shortly after
extubation. He was eventually discharged with stroke rehabilitation completed in the community. Two years later, he has persistent mild dysarthria and focal neurological deficits consistent
with his left MCA stroke.

DISCUSSION
Acute dystonic reactions are involuntary sustained, repetitive
contractions of agonist and antagonist muscle groups.10 They
occur in 2–3% of patients treated with antipsychotics, typically
occurring within 48 h of drug exposure or dose change, and
usually involve cranial, pharyngeal, cervical and axial muscles
with limbs less frequently involved.3 While the propensity of
dopamine-blocking agents to cause acute dystonia is related to
blockade of D2 receptors, the exact mechanism by which dystonia results is unclear.11 Rapid treatment with anticholinergic
agents and removal of offending agents are cornerstones of
management. It is unclear whether hyperacute stroke predisposes patients to acute dystonic reactions, but there have been
rare reports of focal dystonia after motor area infarction.12 In
this case, the patient’s exposure to antipsychotics and prompt
response to intravenous diphenhydramine and benzatropine
were most suggestive of the diagnosis of drug-induced acute dystonic reactions.
Haloperidol, an antipsychotic medication widely used to treat
agitation, has significant activity at type 2 dopamine receptors
and is associated with acute dystonic reactions in 3–10% of
patients.13 Compared with second-generation antipsychotics,
Digby G, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-207215

Reminder of important clinical lesson
haloperidol is similarly efficacious but associated with more sedation, extrapyramidal symptoms and requirement for additional
medications for agitation.13 In fact, a Cochrane Review comparing haloperidol with second-generation antipsychotics found
similar severities of delirium with each, but also found that a
higher dose of haloperidol (>4.5 mg/day) was associated with
increased risk of extrapyramidal adverse effects.14 Furthermore,
a recent clinical care practice guideline suggests that atypical
antipsychotics may be more beneficial than haloperidol at reducing the duration of delirium in adult ICU patients, and should
be the preferred first-line agent.15
In this case, seizures took place shortly after administration of
haloperidol, and while antipsychotic medications can lower the
seizure threshold, haloperidol is thought to be associated with a
relatively lower risk of seizure induction,16 and it is therefore
unclear as to whether this contributed to onset of seizure activity. Another interesting feature of the case was the occurrence of
dystonic reactions after administration of quetiapine and metoclopramide, which may have acted synergistically, and highlights
the importance of careful consideration of drug therapy to minimise side effects. There are several important learning points
from this case. First, the involvement of back arching and leg
muscles in this case make it an atypical presentation of an acute
dystonic reaction and, therefore, more difficult to diagnose.
Second, the patient’s course was complicated by stroke and
status epilepticus, and thus an anchoring bias may have made it
more difficult for caregivers to consider alternative explanations
for the new movements exhibited. For these reasons, careful
clinical analysis of movements and attention to potential causes
is crucial to the correct diagnosis (table 1). Perhaps if this atypical acute dystonic reaction had been recognised and treatment
with benzatropine attempted earlier, these movements may have
resolved more promptly. Had this occurred, perhaps the third
CT scan of the head may have been avoidable, and perhaps
fewer antiepileptics, which can have harmful side effects, particularly in elderly and critically ill patients receiving many
other medications, may have been administered. Finally, it
should be recognised that while haloperidol can be effective in
treating delirium, it is associated with a higher risk of extrapyramidal side effects compared with second-generation antipsychotics, which have been shown to be similarly efficacious in the

management of delirium.13 However, this case also demonstrates that care must be taken when prescribing secondgeneration antipsychotics and metoclopramide to patients at risk
for dystonic reactions, as there is still a risk of extrapyramidal
side effects, the presentation of which might be less
pronounced.
In the ICU, seizures and dystonic reactions can be confused if
careful attention is not paid to the quality of the movements
and potential underlying causes. Patient assessment is often
complicated by the use of sedation, invasive mechanical ventilation, monitoring equipment and the patient’s underlying condition. While diagnosis in this case might have been assisted by
continuous EEG monitoring, this technology is not universally
available around the clock. Furthermore, our patient’s course
was complicated by both seizure poststroke and acute dystonic
reaction, which warranted significantly different treatments.
Careful evaluation of the semiology of movements permitted
proper diagnosis and correct treatment.

Learning points
▸ Critically ill patients may have multiple abnormal
movements, the assessment of which is often complicated
by their critically ill state and associated care.
▸ Acute dystonic reactions are frequently drug related and
typically occur within 48 h of drug exposure or dose change,
and are treated with anticholinergic agents and removal of
the offending drugs.
▸ Haloperidol has similar efficacy in the treatment of delirium
as compared with second-generation antipsychotics, but is
associated with a higher risk of extrapyramidal side effects,
particularly in elderly patients.
▸ Careful evaluation of the semiology of movements may
assist with proper diagnosis and correct treatment when
patients are otherwise difficult to assess, and when EEG is
not available.

Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

Table 1 Abnormal movements in critically ill patients with
neurologic disease
Movement

Characteristics of
movement

Seizure

Rhythmic

Acute
dystonic
reaction

Intermittent spasmodic
or sustained involuntary
contractions of muscles
in the face, neck, trunk,
pelvis, extremities
Sudden, shock-like,
involuntary movements
caused by muscular
contractions or
inhibitions
Flexors predominate in
upper extremity,
extensors in lower
extremity
Asymmetric in stroke

Myoclonus

Paralysis

REFERENCES
1

Duration

Treatment

2

Intermittent
(seconds–hours)
Prolonged and
sustained

Antiepileptics

3

Anticholinergic
agents,
benzodiazepine

4

Very short
(milliseconds–
seconds)

Antiepileptics,
botulinium toxin

5
6
7
8

Fixed, slow to
improve

Physical therapy

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10

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Reminder of important clinical lesson
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Digby G, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-207215