Hyperammonemia presenting as opsoclonus–myoclonus–ataxia–tremor syndrome: A case report

Sandhya Manorenj; Govind Verma

doi:10.4103/aomd.aomd_6_22

CASE REPORT

Year : 2022 | Volume : 5 | Issue : 3 | Page : 198-201

Hyperammonemia presenting as opsoclonus–myoclonus–ataxia–tremor syndrome: A case report

Sandhya Manorenj¹, Govind Verma²
¹ Department of Neurology, Princess Esra Hospital, Deccan College of Medical Sciences, Hyderabad, Telangana, India
² Department of Gasteroenterology, Pace Hospital, Hi Tech City, Hyderabad, Telanagana, India

Date of Submission	08-Feb-2022
Date of Decision	01-Apr-2022
Date of Acceptance	16-May-2022
Date of Web Publication	04-Aug-2022

Correspondence Address:
Prof. Sandhya Manorenj
Department of Neurology, Princess Esra Hospital, Deccan College of Medical Sciences, Hyderabad, Telangana
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aomd.aomd_6_22

Abstract

Opsoclonus myoclonus syndrome (OMS) is a rare autoimmune condition occurring due to Purkinje cell degeneration due to remote aetiology. Most often it occurs as a paraneoplastic syndrome. Here we report a case of opsoclonus-myoclonus–ataxia tremor syndrome in a 60-year-old woman that occurred due to hyperammonemia and she recovered completely with immunotherapy and correction of hyperammonemia. OMS is the first in literature associated with hyperammonemia.

Keywords: Ataxia, hyperammonemia, myoclonus, opsoclonus

How to cite this article:
Manorenj S, Verma G. Hyperammonemia presenting as opsoclonus–myoclonus–ataxia–tremor syndrome: A case report. Ann Mov Disord 2022;5:198-201

How to cite this URL:
Manorenj S, Verma G. Hyperammonemia presenting as opsoclonus–myoclonus–ataxia–tremor syndrome: A case report. Ann Mov Disord [serial online] 2022 [cited 2023 Mar 23];5:198-201. Available from: https://www.aomd.in/text.asp?2022/5/3/0/353461

Introduction

Opsoclonus myoclonus syndrome (OMS) is also called as dancing eyes, dancing feet syndrome. Opsoclonus is characterized by rapid, involuntary eye movements that are chaotic and multidirectional. OMS can be associated with ataxia and tremor also. Clinical manifestation reported in hyperammonemia are encephalopathy, ataxia, seizure, gait abnormality and rarely opsoclonus and myoclonus. Often OMS occurs acutely or subacutely. Most common cause of OMS is paraneoplastic followed by para infectious or idiopathic. OMS associated with hyperammonemia is not reported in literature.

Case Report

A 60-year-old woman with a history of bronchial asthma presented with acute-onset diarrhea for 10 days, fever with vomiting for 5 days, and tremulousness of the whole body for 3 days. She was referred to our hospital from a tertiary care center with a diagnosis of metabolic encephalopathy following acute gastroenteritis. On arrival at the hospital, she had a blood pressure of 120/60 mm Hg, tachycardia of 100 per minute, and temperature of 98°F with altered sensorium. Her Glasgow Coma Scale was score 13 (E4, M5, V3). Neurological examination showed rapid, involuntary, chaotic, and multidirectional eye movements (opsoclonus). In addition, she demonstrated brief jerk-like movements of the limbs (myoclonus); resting, postural, and intention tremor of the hands; and ataxia of both upper limbs and lower limbs with truncal ataxia [Video 1 [Additional file 1]]. Furthermore, she had cerebellar dysarthria. Her ankle jerk reflexes were absent, rest of deep tendon reflexes were normal. Plantars were blilateral flexor response. Her metabolic work including electrolytes, renal function test, liver function tests, blood sugar level, and thyroid profile were in the normal range [Table 1]. She had a hyperammonemia value of 266 μmol/L (normal value, <90 μmol/L), which was evaluated in the fasting state [Table 2]. The test for urea cycle enzyme defects using urinary gas chromatography–mass spectrometry was negative. Brain magnetic resonance imaging (MRI) with contrast was normal. The reverse transcription–polymerase chain reaction test for Covid-19 was negative. In view of her age and thin build, a paraneoplastic cause for opsoclonus–myoclonus–ataxia–tremor syndrome (OMATS) was initially considered. Paraneoplastic and autoimmune profiles in blood (including anti-dipeptidyl-peptidase-like protein 6 antibody test) and the cerebrospinal fluid were negative. Viral markers including human immunodeficiency virus, hepatitis B surface antigen, and anti-hepatitis C virus were negative. The cerebrospinal fluid study was normal. Computed tomography of the abdomen, tumor markers for intestinal malignancy and colonoscopy were normal. Whole-body positron emission tomography (PET) scan was normal. Electroencephalography (EEG) showed diffuse slowing on day 3 [Figure 1]a, and subsequent EEG at 15 days showed normal values [Figure 1]b.

Table 1: Baseline characteristics of the patient

Click here to view

Table 2: Serial ammonia level measurements over days

Click here to view

Figure 1: (a) Electroencephalography (EEG) on day three showing slowing of the theta range and repeat EEG at 2 weeks. (b) Normal EEG

Click here to view

The patient was treated with clonazepam, intravenous methylprednisolone at a dose of 1 g/day for 5 days, followed by maintenance oral steroids along with immunosuppressant (azathioprine at a dose of 1.5 mg/kg bodyweight for 6 months) and a routine regime for the correction of hyperammonemia (rifaximin with essential amino acid supplements). Complete clinical recovery occurred at 3 months. Serum ammonia values were normal. PET scans performed twice at 6-month intervals were negative for malignancies.

Discussion

Opsoclonus–myoclonus syndrome (OMS), first described by Dr. Marcel Kinsbourne in 1962,^[1] is also called dancing eyes-dancing feet syndrome. In addition, tremor and ataxia can occur in OMS. The pathogenesis of OMS is considered to be autoimmune-induced Purkinje cell degeneration.^[2] OMS can occur acutely, as a result of paraneoplastic or parainfectious conditions and can sometimes be idiopathic. Paraneoplastic OMS in adults is frequently associated with small-cell lung cancer and breast cancer, while in children, OMS is exclusively associated with neuroblastomas.^[3],[4] The most common cause of OMS is paraneoplastic or idiopathic conditions.^[5],[6] Clonazepam abates these movement disturbances. Furthermore, a wide spectrum of infections such as viral infections (influenza, varicella, human herpes virus 6, Epstein–Barr virus, cytomegalovirus, coxsackievirus, human immunodeficiency virus, enteroviruses, West Nile virus, and SARS-CoV-2 virus) and bacterial infections (Salmonella, Mycoplasma pneumonia, and Borrelia or infections as a result of post-streptococcal syndrome) can cause OMS.^[5],[7] Infection accounts for only 13% of OMS cases.^[5]

In the present case, acute enteritis followed by gastritis secondary to bacterial infection was considered as the pathophysiology of OMATS. We considered bacterial infection in view of leucocytosis (count of 14,600) with neutrophil predominance at presentation. Baseline blood culture showed isolation of Staphylococcus haemolyticus. There are no reports of OMATS being associated with S. haemolyticus in the literature. However, the infection can cause vomiting, fever, and loose motions, which was the initial presentation in our case. The usual mechanism of pathogenesis is food poisoning and toxin production. We considered it as the true pathogen in view of the patient’s clinical symptoms and response to specific antibiotics (Teicoplanin). Repeat blood culture tests were negative.

In addition, the patient had noncirrhotic persistent hyperammonemia. Studies have revealed that 90% of the hyperammonemia cases in adults is due to cirrhosis, while 10% of the cases is due to noncirrhotic hyperammonemia.^[8],[9] In our patient, hyperammonemia occurred as a result of noncirrhotic hyperammonemia. Urea cycle enzyme defects was normal. Our patient did not have urinary tract infection, which can produce increased urease and hyperammonemia in patients. Our patient did not have similar complaints during her childhood or adolescence, and she was not on any drugs that could induce hyperammonemia (valproic acid, salicylates, sulfadiazine, carbamazepine, ribavirin, and glycine). Therefore, the cause of hyperammonemia was secondary to acquired gastroenteritis, leading to increased metabolism of protein and urea in the colon by the urease bacteria and glutamate degradation in the small intestine by bacteria.

It has been hypothesized that hyperammonemia causes various alterations in the neurotransmitter system responsible for neuronal damage. As a consequence, N-methyl-D-aspartate receptors are activated, leading to decreased phosphorylation of protein kinase C, which results in the activation of sodium–potassium adenosine triphosphatase. The depletion of adenosine triphosphate is responsible for ammonia toxicity and is attributed to seizures in acute hyperammonemia.^[10] The other manifestations of hyperammonemia are irritability, confusion, ataxia, gait abnormality, encephalopathy, myoclonus, and opsoclonus.^[11],[12] Our patient had these clinical manifestations. Brain MRI usually shows diffusion restriction in the insular cortex and cingulate gyrus in acute hyperammonemia with encephalopathy, which is reversible. On the other hand, chronic hyperammonemia due to cirrhosis or urease cycle enzyme defects causes hyperintensity changes in the globus pallidus, thalamus, and cortices (parietal, temporal, occipital, and frontal cortices), as observed with T2-Fluid-attenuated inversion recovery.^[13] No abnormalities were observed in our patient on MRI. This may be due to the short duration of the illness, the patient’s blood ammonia level, and early medical intervention on day three of the illness. The prevalence of MRI abnormalities in hyperammonemia is not exactly known.

To the best of our knowledge, ours is the first report on the association of hyperammonemia with infective gastroenteritis presenting as OMATS. Metabolic encephalopathy was initially considered in view of hyperammonemia; however, mild encephalopathy subsequent to neurological examination helped diagnose OMATS, which led to timely immunotherapy and a dramatic response in 3 days.

Conclusion

Hyperammonemia associated with acute infective gastroenteritis can mimic metabolic encephalopathy. Proper neurological examination will help in diagnosing this rare association of OMATS with hyperammonemia. Treatment in such an association includes immunotherapy, measures to lower ammonia, and symptomatic treatment for OMATS (clonazepam). Paraneoplastic OMATS should be considered in older adults. In addition, it should be ruled out using a serial whole-body PET scan before labelling the condition as parainfectious OMATS, as in the present case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Written valid and informed consent was obtained from the patient for video recording, and both print and online publication of the videos.

Acknowledgements

Nil.

Author contribution

Sandhya Manorenj: Conception, clinical examination, literature review, video recording, and video editing. Writing the first draft of the article, review and critique, and final approval of the version to be published. Govind Verma: literature review, review and critique, and final approval of the version to be published.

Ethical compliance statement

The authors confirm that the approval of an institutional review board was not required for this work. They also confirm that they have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry 1962; 25: 271-6.
2.	Scarff JR, Iftikhar B, Tatugade A, Choi J, Lippmann S. Opsoclonus myoclonus. Innov Clin Neurosci 2011;8:29-31.
3.	Bataller L, Graus F, Saiz A, Vilchez JJ, Spanish opsoclonus-myoclonus study group. Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonus-myoclonus. Brain 2001;124:437-43.
4.	Luque FA, Furneaux HM, Ferziger R, Rosenblum MK, Wray SH, Schold SC Jr, et al. Anti-Ri: An antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991;29:241-51.
5.	Klaas JP, Ahlskog JE, Pittock SJ, Matsumoto JY, Aksamit AJ, Bartleson JD, et al. Adult-onset opsoclonus-myoclonus syndrome. Arch Neurol 2012;69:1598-607.
6.	Dalmau J, Rosenfeld MR, Guichard M, Vignon G, Guichard M, Cabanne F, et al. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008;7:327-40.
7.	Emamikhah M, Babadi M, Mehrabani M, Jalili M, Pouranian M, Daraie P, et al. Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: Case series and review of literature. J Neurovirol 2021;27:26-34.
8.	Upadhyay R, Bleck TP, Busl KM. Hyperammonemia: What urea-lly need to know: Case report of severe noncirrhotic hyperammonemic encephalopathy and review of the literature. Case Rep Med 2016;2016:8512721.
9.	Olde Damink SW, Jalan R, Dejong CH. Interorgan ammonia trafficking in liver disease. Metab Brain Dis 2009;24:169-81.
10.	Llansola M, Rodrigo R, Monfort P, Montoliu C, Kosenko E, Cauli O, et al. NMDA receptors in hyperammonemia and hepatic encephalopathy. Metab Brain Dis 2007;22:321-35.
11.	Vaquero J, Chung C, Cahill ME, Blei AT. Pathogenesis of hepatic encephalopathy in acute liver failure. Semin Liver Dis 2003;23:259-69.
12.	Rosenberg C, Rhodes M. Hyperammonemia in the setting of Roux-en-Y gastric bypass presenting with osmotic demyelination syndrome. J Community Hosp Intern Med Perspect 2021;11:708-12.
13.	U-King-Im JM, Yu E, Bartlett E, Soobrah R, Kucharczyk W. Acute hyperammonemic encephalopathy in adults: Imaging findings. AJNR Am J Neuroradiol 2011;32:413-8.