Haloperidol-induced isolated lingual dystonia
- 1 Department of Psychiatry and Behavioral Sciences, University of Texas John P and Katherine G McGovern Medical School, Houston, Texas, USA
- 2 Louis A Faillace Department of Psychiatry and Behavioral Sciences, UTHealth Harris County Psychiatric Center, Houston, Texas, USA
- Correspondence to Jeff Wang Jin; jeff.w.jin@uth.tmc.edu
Abstract
A 28-year-old woman presenting with agitation and mania with psychotic features developed symptoms of isolated lingual dystonia shortly after the initiation of a haloperidol concentrate regimen.
Background
Dystonia is the involuntarily maintained contraction of muscle that may lead to abnormal posturing, twisting, tremors and irregular movements.1 The original proposed pathophysiology of dystonia was dysfunction of the basal ganglia, especially lesions in the putamen and globus pallidus. However, in some cases the absence of neurodegeneration and presence of lesions external to the basal ganglia have suggested that dystonic reactions may result from abnormal connectivity within a normal structured brain.1 While tongue involvement is a common manifestation of dystonia,2–4 cases of isolated lingual dystonia are rarely recorded in the literature.
Dystonia can be divided into primary and secondary aetiologies. Primary aetiologies include familial and sporadic causes, but other sources must be first ruled out.1 Secondary aetiologies include head injury (hypoxia),1 medication effects (antipsychotics, antiemetics, antiepileptics)1 and neurological disease (Wilson’s disease).5 Other less common secondary causes include vascular disease (stroke, arteriovenous malformation, haemorrhage), infective sources (neuroacanthosis)6 and toxic aetiologies.7
Drug-induced dystonia can result from the administration of several medications including antipsychotics, antiemetics and antiepileptics. However, it is most recognised as an extrapyramidal side effect of first-generation and second-generation antipsychotics.8 These effects are due to rapid changes in antagonism of dopamine D2 receptors which typically arise after either a substantial increase in dose or receptor affinity (potency) of the medication.9 It is suggested that abnormal medium spiny neuron activity, inhibition of acetylcholine release at striatal interneurons and decreased activation of fast-spiking GABAergic interneurons may contribute to the dystonic mechanism resulting from dopamine D2 antagonism.8 While several models with common themes have been proposed to illustrate the pathophysiology of dystonia,10–14 specific pathways for dystonia and its variants need further investigation.
Due to the expanding aetiologies of dystonia, the number of available treatments continue to increase. Medications such as anticholinergics, antihistamines, dopaminergics, GABAergics and muscle relaxants have shown efficacy.15 Botulinum neurotoxin, surgical ablation and neuromodulation interventions including deep brain stimulation (DBS) may also be used as treatment.15
We report a rare case of isolated lingual dystonia secondary to the administration of haloperidol, a first-generation high potency antipsychotic. The case demonstrates the possibility of quick symptomatic resolution with intramuscular (IM) treatments of dystonia as opposed to oral (PO) alternatives.
Case presentation
A 28-year-old woman with a history of anxiety and prior psychiatric admission presented to the hospital with agitation and mania with psychotic features. On presentation, the patient was given an intramuscular dose of haloperidol 5 mg, lorazepam 2 mg and diphenhydramine 50 mg. The patient was started on a daily haloperidol concentrate 10 mg regimen for mood and psychosis.
Within 48 hours of admission, the patient reported ‘tongue twisting’. When further prompted during the interview, the patient’s tongue was observed either pressed against her teeth or positioned between her teeth during speech. Dysarthria was noted at the time, but the patient did not report any additional dystonic features or associated symptoms. Within two additional hours, the patient reported both dysarthria and dysphagia as she was seen attempting to regurgitate food. The patient’s tongue was observed attempting to roll back into her throat by nursing staff.
The patient had endorsed a history of isolated lingual dystonia after taking psychiatric medications in Africa several years ago. During this time, she described three prior episodes of her tongue ‘rolling back into the throat’ and becoming ‘stiff’ after taking an unknown antipsychotic medication. She endorsed that the symptoms disappeared after cessation of the medication. She reported that drinking cold water rarely alleviated symptoms while chewing significantly worsened symptoms. She denied past brain injury, recent use of illicit substances and recent viral, fungal or bacterial infections. Additionally, she reported that none of her family members have experienced similar symptoms and denied any familial history of Wilson’s disease, vascular disease and isolated lingual dystonia. The neurological examination was normal—showing intact cranial nerves with normal finger-to-nose testing, heel-shin testing, rapid alternating movements, tandem gait, muscle tone and sensation. No abnormal eye movements were observed, and the patient did not exhibit anxiety, restlessness, intense staring or other signs suggestive of an oculogyric crisis. Furthermore, dystonic lingual movements were present, but no other abnormal movements such as chorea, athetosis, myoclonus, tremors, tics, parkinsonism and akinesias were observed. The rest of the physical examination demonstrated no additional abnormalities.
The comprehensive metabolic panel, complete blood count and thyroid-stimulating hormone results were within normal ranges. The lipid panel showed a mild elevation of low-density lipoprotein (LDL) cholesterol at 107 mg/dL (N: 0–99 mg/dL). The HIV antibody and rapid plasma reagin (RPR) syphilis screens were non-reactive. The urine pregnancy test was negative. The urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, phencyclidine, cannabis and opioids was negative.
Differential diagnosis
Given the lack of any other presenting symptoms, isolated lingual dystonia was the most considered differential diagnosis secondary to either a medication-induced, substance-induced, infective or metabolic aetiology. Additionally, Wilson’s disease and other neurodegenerative disorders with a history of abnormal movements were considered as well. Besides a mild elevation of LDL cholesterol, the obtained laboratory studies were in normal reference range and vital signs were consistently stable. A lack of laboratory study abnormalities paired with a thorough medical history eliminated infective, substance, metabolic and neurodegenerative aetiologies as sources of the observed focal dystonia. The presentation is most likely an isolated dystonic reaction resulting from administration of haloperidol.
Treatment
Initially, sensory tricks (chewing gum, neck pressure) were attempted without symptom improvement. After, benztropine 1 mg PO was administered but failed to immediately reduce symptoms. Within another 15 min, diphenhydramine 50 mg IM was administered.
Outcome
The patient had full resolution of symptoms within 1 hour. She is not deceased, and follow-up is not necessary given her clinical resolution. She was advised to consult a psychiatrist if symptoms return.
Discussion
Isolated lingual dystonia (ILD) is a localised dystonic reaction that does not involve any additional areas of abnormal dystonic symptoms. While the isolated dystonic variant shares similar aetiologies with oromandibular dystonia,8 additional variants of speech-induced16 17 and task-induced lingual dystonia18 have been reported in the literature. Compared with ILD, these variants have more chronic progressive onsets (weeks to years) and are characterised by a longer duration to treatment response.16–18 Additionally, some cases report the efficacy of sensory tricks such as chewing17 19 or jaw clenching17 in symptomatic alleviation.
There are no studies analysing predisposition in ILD specifically; however, it may share similar risk factors with dystonia as it is classified as a variant subtype. For dystonia and its variants, it remains unclear why it selectively occurs in some patients but not others. In addition to various direct aetiologies, other factors may predispose some patients to an increased probability of dystonic reactions. Defazio et al suggested that both environmental and genetic factors may be associated with the aetiology of dystonia. Facial trauma with loss of consciousness and a family history of dystonia/postural tremor increased the risk of developing idiopathic adult-onset dystonia.20 A positive association was also noted between local body injury and dystonic developments of the same injury area. Additionally, hypertension and smoking cigarettes appeared to have a protective effect against dystonia.20 Siokas et al further suggested that the genetic component of dystonia was strongly associated with pathogenic variants of the TOR1A and BDNF genes.21 It is proposed that these variants induce dystonia due to altered normal gene function, but further investigation is needed.
On narrative review, six additional cases of ILD were found.22–27 Including the present case, a total of seven cases have been reported in the literature (table 1). Some similarities in symptom presentation were noted between the current case and previous case reports. Like the present case, one case reported specific tongue twisting movements22 and two cases reported both dysarthria and dysphagia.23 27 Additionally, one case failed to demonstrate improvements in involuntary movements with food manipulation in the oral cavity—consistent with the present case.26 The similarity in these cases suggests that tongue twisting, dysarthria and dysphagia may be more common features seen in ILD.
Review of treatment efficacy in medication-induced isolated lingual dystonia
| Author | Sex | Age (years) | Medication | Treatment | Outcome | Symptom description |
| Reecer et al 22 | M | 18 | Prochlorperazine | Diphenhydramine (intramuscular) | Resolution of symptoms within 15 min | Curling and twisting of the tongue without relaxation Cramping with slow side-to-side movement |
| Gair et al 23 | F | 1.5 | Pimozide | None | Resolution of symptoms without pharmacological intervention | Drooling, tongue thrusting, no observed body tremors |
| van Pelt-Sprangers et al 24 | F | 56 | Capecitabine | Biperiden (intravenous) | Resolution of symptoms within 20 min without reappearance continuing intravenous anticholinergic for 3 days | Numbness and abnormal movements of the tongue Difficulty swallowing, speaking, and some airway obstruction |
| Tsai25 | F | 38 | Ziprasidone | Benztropine (intramuscular, oral) | Resolution of symptoms within 25 min on intramuscular injection without reappearance continuing oral anticholinergic for 3 days | Strange sensation of the tongue with loss of words Visibly protruding tongue with marked dysphonia |
| Verma and Shettigar26 | F | 18 | Metoclopramide | Promethazine (intramuscular) Trihexyphenidyl (oral) | Gradual improvement single dose of intramuscular promethazine and daily oral anticholinergic with normalisation within 3 days | Persistent vertical positioning of the tongue Associated with dysarthria and difficulty swallowing |
| Aggarwal et al 27 | M | 60 | Lithium | Trihexyphenidyl (oral) |
Some symptomatic improvement with lithium withdrawal and addition of anticholinergic | Involuntary movements of tongue Exaggerated with speaking and food manipulation in the oral cavity |
| Jin et al (Present Case) |
F | 28 | Haloperidol | Diphenhydramine (intramuscular) | Resolution of symptoms within 15 min | Tongue twisting, pressed against teeth Dysarthria, dysphagia No improvement with sensory tricks (chewing gum, neck pressure) |
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Intramuscular and intravenous administration routes showed a shorter duration of symptom resolution in comparison to oral preparations.
Treatments of medication-induced isolated lingual dystonia were comparable to those of acute dystonic reactions. Of the six additional cases, five showed medications with dopamine antagonist properties as aetiologies for ILD.22 23 25–28 While the relationship between capecitabine and dopamine signalling is not fully understood, capecitabine does not have any well-known dopamine effects.24 For pharmacological treatment, three cases used anticholinergics, one used an antihistamine, one used a combination of both and one case resolved without pharmacological intervention (table 1). Additionally, for the route of treatment administration, one case used intramuscular, one case used intravenous, one case used oral and two cases used an intramuscular and oral combination (table 1). Intramuscular and intravenous administrations produced the fastest resolution of symptoms (within minutes) compared with oral administrations (table 1). This is reflected in the current case as the use of oral benztropine did not initially resolve the patient’s symptoms, prompting the subsequent administration of intramuscular diphenhydramine.
Although no cases of isolated lingual dystonia have reported life-threatening effects, failure to initiate timely and sufficient treatment may result in potentially harmful clinical consequences. The major concern of uncontrolled tongue movements involves the obstruction of the oropharynx. The unpredictable nature of lingual dystonia may result in airway blockage—similarly seen in obstructive sleep apnoea. Although unlikely, the precipitation of sleep apnoeic sequelae such as airway crowding, decreased oxygen saturation and neurocognitive impairment cannot be completely disregarded.29 Additionally, oropharynx obstruction may induce choking and dysphagia as seen in our patient.30 Lingual dystonia is typically not regarded as an emergency; however, inadequate management of symptomology may result in dangerous effects. Thus, rapid symptomatic relief with intravenous and intramuscular medications should be considered over oral preparations to prevent the development of avoidable clinical consequences.
Some limitations to this case include the lack of copper levels, ceruloplasmin levels and video of the dystonic event. The patient denied any similar symptoms in family members, family history of Wilson’s disease and history of liver or ocular abnormalities. On review of other local electronic medical records, it was also revealed that the patient has never had a copper or ceruloplasmin laboratory study drawn during previous hospital and outpatient visits—suggesting a low suspicion for Wilson’s disease. Although they are not common laboratory studies drawn at our hospital, copper and ceruloplasmin values would have been effective in ruling out the diagnosis of Wilson’s disease. Additionally, video of the dystonic episodes was unable to be obtained due to the brevity of the events prior to resolution. Unfortunately, informed consent was obtained after the symptoms had resolved. This information would help better illustrate and classify the lingual movements in ILD.
While isolated lingual dystonia secondary to medications has been under-reported in the literature, the few established cases report efficacy in symptom resolution with antihistamines and anticholinergics with a preference for an intramuscular route of administration. While clinical management of isolated lingual dystonia does not appear to differ from the management of acute dystonic drug reactions, further investigation into additional unknown aetiologies and non-pharmacological treatments may be warranted.
Learning points
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Medication-induced isolated lingual dystonia should be managed with intramuscular or intravenous preparations of antihistamines and anticholinergics.
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Medication-induced isolated lingual dystonia may result from drugs without known dopamine antagonism.
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Prompt management of isolated lingual dystonia is necessary to avoid potentially life-threatening risks of oropharyngeal obstruction.
Ethics statements
Patient consent for publication
Footnotes
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Contributors JWJ obtained patient consent and led the design, writing and publication of the manuscript. AC assisted in obtaining consent and helped write the paper. NK assisted in writing and editing the paper. AH helped edit the manuscript and provided guidance regarding case direction and clinical implications.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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