A fatal disease hidden behind a common symptom: Neuromyelitis optica spectrum disorder

Vishal Chandra Sharma; Anisha Umashankar

doi:10.4103/injms.injms_99_21

CASE REPORT

Year : 2022 | Volume : 13 | Issue : 2 | Page : 124-126

A fatal disease hidden behind a common symptom: Neuromyelitis optica spectrum disorder

Vishal Chandra Sharma, Anisha Umashankar
Department of General Medicine, Kasturba Medical College, MAHE, Manipal, Karnataka, India

Date of Submission	26-Aug-2021
Date of Decision	21-Sep-2021
Date of Acceptance	21-Sep-2021
Date of Web Publication	21-Mar-2022

Correspondence Address:
Dr. Vishal Chandra Sharma
Plot No. 59, Sharma Bhavan, Road No. 3, Chandrapuri Colony, L.B. Nagar, Hyderabad - 500 074, Telangana
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injms.injms_99_21

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system. Recently, a number of clinical features have been identified in the diagnosis, and this disorder has been expanded to include a wider spectrum. It is important to have knowledge of these syndromes to diagnose this condition. One such presentation is intractable vomiting and hiccoughs, which is categorized as area postrema syndrome (APS) and is often misdiagnosed as a digestive disorder. We present a case of young female presenting with unresolving vomiting and hiccoughs. Magnetic resonance imaging done showed lesions in the dorsal medulla, suggestive of APS. A positive immunoglobulin G aquaporin-4 antibody confirmed the diagnosis of NMOSD. With this case report, we try to reiterate the importance of knowing the varied presentations of NMOSD and vigilance in identifying that a common symptom such as vomiting/hiccough can be due to an uncommon disorder.

Keywords: Area postrema, intractable hiccough, intractable vomiting, neuromyelitis optica spectrum disorder

How to cite this article:
Sharma VC, Umashankar A. A fatal disease hidden behind a common symptom: Neuromyelitis optica spectrum disorder. Indian J Med Spec 2022;13:124-6

How to cite this URL:
Sharma VC, Umashankar A. A fatal disease hidden behind a common symptom: Neuromyelitis optica spectrum disorder. Indian J Med Spec [serial online] 2022 [cited 2023 Mar 31];13:124-6. Available from: http://www.ijms.in/text.asp?2022/13/2/124/340035

Introduction

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system, which is considered a mimic of multiple sclerosis (MS). It was predominantly found to present as transverse myelitis and optic neuritis which was referred previously as Devic's disease. However, with the advent of biomarkers such as aquaporin-4 (AQP-4) and MOG antibodies, various other clinical presentations have been found and is now included as a broad term, NMO spectrum disorder (NMOSD). NMOSD now includes area postrema syndrome (APS), diencephalic, and acute brainstem syndrome apart from optic neuritis and transverse myelitis.

Case Presentation

We present a case of an 18-year-old female who came with complaints of unresolving vomiting and hiccoughs. She had been evaluated by a gastroenterologist and had undergone upper gastrointestinal scopy which showed a Mallory Weiss tear. She was referred to us as symptoms persisted. The patient presented with 20 days of vomiting and 5 days of intractable hiccoughs which was present throughout the day. Vomiting was nonbilious, small quantities with 4–5 episodes per day and was not associated with fever, diarrhea, abdominal pain, and headache. She also had a history of swaying while walking but not conformed to a particular side. There was no history suggestive of cranial nerve involvement. She did not have any history of weakness or sensory, bowel, and bladder disturbances. On examination, the patient's vitals were normal. Nervous system examination revealed normal higher mental functions. Cranial nerve examination was normal. Motor system examination showed normal tone and power in all four limbs. She had gait ataxia; however, other cerebellar signs were negative. Sensory system examination was normal with no signs of meningeal irritation.

Investigations revealed normal blood counts and serum electrolytes. HIV serology was negative. Magnetic resonance imaging (MRI) showed hyperintensity in the dorsal part of the medulla in T2-weighted imaging [Figure 1] and hypointensity in T1-weighted imaging [Figure 2]. Postgadolinium contrast nonuniform enhancement of the area in the medulla was noted [Figure 3]. AQP-4 immunoglobulin G (IgG) antibody sent was positive.

Figure 1: Sagittal and axial images showing hyperintensity in T2-weighted imaging in dorsal medulla

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Figure 2: Hypointensity in dorsal part of medulla in T1-weighted imaging

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Figure 3: Postcontrast nonuniform, peripheral enhancement of the lesion

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The patient was started on intravenous steroids with 1 g methylprednisolone which was given for a total of 5 days and then continued as oral 1 mg/kg. The patient symptoms showed improvement on the 3^rd day of pulse steroids. She was continued on oral steroids and discharged. On follow-up, her symptoms had improved and she was started on immunosuppressants with azathioprine. Her follow-up MRI after 3 weeks showed a resolution of the previous lesions [Figure 4]. In further follow-up visits, she did not have any recurrence of symptoms and was clinically better.

Figure 4: Magnetic resonance imaging showing resolution of the lesion 3 weeks posttreatment

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Discussion

NMOSD is an inflammatory demyelinating disease of the central nervous system. It was initially labeled as Devic's disease with presentation of transverse myelitis and optic neuritis. With the discovery of autoantibody specific to the disease, the clinical manifestations have been expanded to include other syndromes which now form a part of core clinical characteristic in the diagnosis of NMOSD. Our case presented with intractable vomiting and hiccoughs which form a part of APS of the NMOSD. In a recent study analyzing the collective database of patients in Japan, the UK, and the USA, the frequency of isolated APS at disease onset was found to be 7.1%, 8.7%, and 10.3%, respectively.^[1] Considering the symptoms of vomiting and hiccoughs, patients often may contact a gastroenterologist for it and are often misdiagnosed. The study showed that 44 of the 430 patients presented initially to gastroenterologists and underwent extensive workup without any diagnosis with 20% being given an incorrect diagnosis for their APS.^[1] In a study done in China, in 12 patients of NMOSD, it was observed that 83% of the patients were positive for serum AQP-4 antibodies (AQP4-Abs) and 60%–70% patients had medullary lesions on MRI brain, involving the dorsomedial and area postrema regions.^[2] In a study in South India, NMOSD constituted 13.9% of all demyelinating disorders, with a prevalence of 2.6/100,000.^[3]

In 2004, the discovery of AQP4-IgG as a specific biomarker of NMO allowed its distinction from MS. This discovery led to the recognition that patients can have more limited forms of the disease or symptoms beyond the optic nerve and spinal cord (e.g. APS), resulting in the current nosology of NMOSDs.^[4],[5],[6] AQP4 is a bidirectional water channel found at highest concentrations in end feet of astrocytes in the perivascular and peri-pial regions.^[7] NMOSD typically affects area where AQP4 expression is found in high levels like typically involving areas around circumventricular organs and areas adjacent to third and fourth ventricle (dorsal medulla, area postrema).^[8] MRI of our patient showed lesions involving dorsal medulla which is typical of NMOSD, and the diagnosis was confirmed with positive AQP4-IgG antibody. A high level of suspicion is required so that the diagnosis of NMOSD is not missed. In the absence of typical MRI findings, a cutoff of 48 h as the minimum duration of symptoms after excluding other possible etiologies was used to increase the specificity of the diagnosis of APS. An updated diagnostic criteria for NMOSD was published in 2015, for both AQP4-Ab–positive and negative cases with core clinical features including optic neuritis, acute transverse myelitis, area postrema, brainstem syndrome, diencephalic, and cerebral syndrome.^[6],[9]

The treatment of acute attacks consists of intravenous methylprednisolone for at least 3–5 consecutive days. Patients who fail to recover with intravenous steroids may need escalation of treatment with plasma exchange or intravenous immunoglobulin.

NMOSD is a relapsing disorder rather than a monophasic disorder; hence, it is important to initiate maintenance therapy with immunosuppressants and close follow-up of the patients. The immunosuppressants most commonly used are azathioprine, mycophenolate mofetil, and rituximab. The choice of immunosuppression may depend on local availability, cost, and duration of concomitant oral steroids needed while the immunosuppressant takes effect. Our patient was treated with intravenous methylprednisolone (1 g for 5 days) and tapering dose of steroids with azathioprine for maintenance therapy on follow-up. There was symptomatic improvement posttreatment and MRI done 3 weeks posttreatment showed resolution of the lesions of the dorsal medulla.

Conclusion

It is important to consider a neurological cause for a common symptom such as vomiting and hiccough, especially as the primary medical contact for these patients is usually a general physician or gastroenterologist. The delay in diagnosis can lead to a worsening of neurological deficits, and it is imperative to diagnose early and initiate treatment. Our case report highlights the importance of identifying a serious neurological illness presenting with a nonspecific symptom such as vomiting and the importance of early initiation of therapy in the resolution of acute attack and the prevention of relapses.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Shosha E, Dubey D, Palace J, Nakashima I, Jacob A, Fujihara K, et al. Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology 2018;91:e1642-51.
2.	Jin X, Pei S, Liu Y, Li X. Clinical analysis of neuromyelitis optica presenting as intractable nausea, vomiting and hiccups. Int J Neurosci 2017;127:854-8.
3.	Pandit L, Kundapur R. Prevalence and patterns of demyelinating central nervous system disorders in urban Mangalore, South India. Mult Scler 2014;20:1651-3.
4.	Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet 2004;364:2106-12.
5.	Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005;202:473-7.
6.	Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-89.
7.	Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP. Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 1997;17:171-80.
8.	Kim HJ, Paul F, Lana-Peixoto MA, Tenembaum S, Asgari N, Palace J, et al. MRI characteristics of neuromyelitis optica spectrum disorder: An international update. Neurology 2015;84:1165-73.
9.	Mealy MA, Wingerchuk DM, Greenberg BM, Levy M. Epidemiology of neuromyelitis optica in the United States: A multicenter analysis. Arch Neurol 2012;69:1176-80.