A case of metoclopramide-induced oculogyric crisis in a 16-year-old girl with cystic fibrosis.

Abstract: Oculogyric crisis is a neurologic reaction characterized by bilateral dystonic elevation of visual gaze as well as hyperextension of the neck. This reaction is most commonly explained as an adverse effect of numerous medications, such as dopamine receptor blocking agents or neuroleptic medications and traditional antipsychotic or antiemetic drugs, such as prochlorperazine or metoclopramide. A case of oculogyric crisis induced by metoclopramide is described in this paper.

Key Words: oculogyric crisis, metoclopramide, dystonic reaction

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Oculogyric crisis is a neurologic reaction characterized by bilateral dystonic elevation of visual gaze as well as hyperextension of the neck. (1) This reaction is most commonly explained as an adverse effect of numerous medications, such as dopamine receptor blocking agents or neuroleptic medications and traditional antipsychotic or antiemetic drugs, such as prochlorperazine or metoclopramide. (1-6) A case of oculogyric crisis induced by metoclopramide is described in this case report.

Case Report

The patient was a 16-year-old girl statuspost bilateral lung transplant for cystic fibrosis with a history of transplant rejection and severe peripheral neuropathy secondary to malnutrition and tacrolimus. She had recently undergone a Nissen fundoplication procedure, and was admitted for poor oral intake with a one-week history of nausea, vomiting, and headaches, as well as dizziness and blurred vision. In the month before this admission, she had been hospitalized for evaluation of her neuropathy and was started on oxcarbazepine, gabapentin, and methadone. Electroencephalogram (EEG), magnetic resonance imaging (MRI) and computed tomography (CT) of the brain had been unremarkable. The oxcarbazepine was discontinued during that hospital stay, and she was later seen as an outpatient for severe myoclonic jerking, possibly due to the abrupt discontinuation of this agent. After being admitted to an outside hospital for evaluation of abnormal movements, her methadone and gabapentin were both tapered, and she was transferred to Duke University Medical Center. She was started on metoclopramide 5 mg p.o. q.i.d. daily because of her ongoing problems with nausea and vomiting. Thirty-six hours later, she complained of a sudden onset inability to move her eyes. On examination, she was cachectic, anxious, and had a bilateral fixed upward gaze. Pupils were equal round and reactive to light bilaterally with a visual acuity of 20/400 and no photophobia. There was no vertical or horizontal nystagmus and no blurring of vision, which was restricted to the upper visual fields. Examination was otherwise notable for asterixis. Diphenhydramine was administered 25 mg IV once, with rapid and complete resolution of the dystonic reaction. Labs were notable for a calcium of 8.7, phosphorus of 4.1, magnesium 2.5, alkaline phosphatase 259, AST 44, ALT 102, and ammonia level of 3. Chem-7 was normal with the exception of a bicarbonate level of 29, and CBC revealed a WBC of 2.1, hemoglobin 9.0, and hematocrit of 28. A noncontrast CT of the head was negative for stroke or mass. The metoclopramide was discontinued, and she experienced no further dystonic reactions during the remainder of her hospitalization.

Discussion

We present the case of a young patient who experienced oculogyric crisis following regular administration of metoclopramide for nausea, vomiting, and poor oral intake following a recent Nissen fundoplication. There have been few cases published on oculogyric crisis in general, but several of these cases have been notable for the role of metoclopramide in inducing this reaction. (6-9) In one notable and similar case, a 21-year-old girl developed oculogyric crisis after receiving five oral doses of metoclopramide at 10 mg. (6) In our case, as well as in the case of the 21-year-old girl, the dystonic reaction was relieved quickly by administration of diphenhydramine. (6) One retrospective study in France demonstrated the relative frequency of extrapyramidal symptoms of children in reaction to metoclopramide, with oculogyric crisis cases specifically comprising 13 of 81 total cases of acute dystonia occurring in 184 pediatric patients with metoclopramide poisoning. (9) The dose threshold for extrapyramidal side effects was highly variable in the above studies, making a cut-off of appropriate metoclopramide dosing very difficult. However, it is interesting to note from individual cases, as well as in our own patient, that the pattern involved multiple administrations of 5 or 10 mg of metoclopramide accumulated over more than 24 hours before observation of the dystonic side effects.

Oculogyric crisis has also been noted as a reaction to other classes of medications as well.

One case report details oculogyric crisis accompanied by torticollis 26 hours following IM administration of haloperidol lactate in a 22-year-old woman enrolled in a study of the effects of neuroleptic medications on stable patients with schizophrenia. This dystonic reaction was quickly reversed with an IM dose of benztropine. (4) It was noted in that case study that sudden onset of such symptoms is not uncommon 12 to 24 hours after starting the offending medication, due in this case to accumulation of toxic metabolites of the high-potency neuroleptic. (4) Oculogyric crisis has also been noted as an adverse effect of carbamazepine in a 32-year-old male patient with uncontrolled complex partial epilepsy receiving both carbamazepine and divalproex sodium, with immediate resolution following downward titration of the former medication. (5) Other cases have reported similar problems with phenothiazines. (2,3) Bumpass and Knoll (10) have also proposed a role of emotional stress arousal in combination with such medications as hastening the onset or exacerbation of oculogyric crisis in certain patients based on a psychophysiological model.

Conclusion

In this case report, we present a clinical scenario involving a young woman adversely affected by the dystonic side effects of metoclopramide, in the form of a severe neurologic and ophthalmologic reaction which resolved quickly with diphenhydramine.

It is clear that complaints of visual disturbances in patients taking any of the medications mentioned in the above discussion should be taken seriously and evaluated further for manifestation of other extrapyramidal symptoms as well as consideration of oculogyric crisis.

References

1. Fraunfelder FW, Fraunfelder FT. Adverse ocular drug reactions recently identified by the National Registry of Drug-Induced Ocular Side Effects. Ophthalmology 2004;111:1275-1279.

2. Schumock GT, Martinez E. Acute oculogyric crisis after administration of prochlorperazine. South Med J 1991;84:407-408.

3. Skorin L Jr, Onofrey BE, DeWitt JD, Phenothiazine-induced oculogyric crisis. J Am Optom Assoc 1987;58:316-318.

4. Jhee SS, Zarotsky V, Mohaupt SM, et al. Delayed onset of oculogyric crisis and torticollis with intramuscular haloperidol. Ann Pharmacother 2003;37:1434-1437.

5. Gorman M, Barkley GL. Oculogyric crisis induced by carbamazepine. Epilepsia 1995;36:1158-1160.

6. Edwards M, Koo MW, Tse RK. Oculogyric crisis after metoclopramide therapy. Optom Vis Sci 1989;66:179-180.

7. Faura A, Canet J, Gallart L. [Oculogyric crisis associated with the use of metoclopramide]. Rev Esp Anestesiol Reanim 1990;37:185-186.

8. Berkman N, Frossard C, Moury F. [Oculogyric crisis and metoclopramide]. Bull Soc Ophtalmol Fr 1981;81:153-155.

9. Cezard C, Nisse P, Quaranta S, et al. [Acute dystonia from metoclopramide in children]. Therapie 2003;58:367-370.

10. Bumpass ER, Knoll JL III. Emotional factors in oculogyric crisis. J Nerv Ment Dis 1982;170:366-370.

Emil Lou, MD, PhD. and Nuhad Abou-Zeid, MD

From the Departments of Medicine and Neurology, Duke University Medical Center, Durham, NC.

Reprint requests to Emil Lou, MD, PhD, Box 31117, DUMC, Durham, NC 27710. Email: [e-mail]

Accepted April 26, 2006.

RELATED ARTICLE: Key Points

* Oculogyric crisis is a neurologic reaction which manifests as a dystonia which can be induced by various classes of medications.

* Metoclopramide is an example of one such medication which can lead to oculogyric crisis.

* Dystonia resulting from metoclopramide can be rapidly reversed by diphenhydramine.