|Year : 2019 | Volume
| Issue : 4 | Page : 222-224
Area postrema syndrome: A lesser known variant of neuromyelitis optica spectrum disorder
Gaurav Kumar Mittal, Shilpa Sekhar, John Jacob Mathew, Jennifer Singhdev
Department of Neurology, St. Stephen's Hospital, New Delhi, India
|Date of Submission||24-Sep-2019|
|Date of Acceptance||03-Oct-2019|
|Date of Web Publication||06-Nov-2019|
Gaurav Kumar Mittal
Department of Neurology, St. Stephenfs Hospital, New Delhi - 110 054
Source of Support: None, Conflict of Interest: None
One of the most specific presentations of neuromyelitis optica spectrum disorders (NMOSDs) is area postrema syndrome (APS). Although NMOSDs are now being increasingly encountered, APS is rarely reported in literature. With the emergence of the ever-expanding spectrum of neuromyelitis optica (NMO) comes various challenges in the prompt recognition, confirmation, and swift initiation of the therapy. Although with the new consensus criteria of the International Panel of NMO Diagnosis 2015, the earlier challenges of diagnosis have been removed to a great extent, still there is a long road ahead in the widespread dissemination of the current knowledge of NMOSD among health-care professionals in India. We hereby report a case of APS in a young female with endeavor to increase the awareness of this peculiar kind of presentation from India.
Keywords: Area postrema syndrome, nausea, neuromyelitis optica spectrum disorder, vomiting, hiccups
|How to cite this article:|
Mittal GK, Sekhar S, Mathew JJ, Singhdev J. Area postrema syndrome: A lesser known variant of neuromyelitis optica spectrum disorder. Indian J Med Spec 2019;10:222-4
|How to cite this URL:|
Mittal GK, Sekhar S, Mathew JJ, Singhdev J. Area postrema syndrome: A lesser known variant of neuromyelitis optica spectrum disorder. Indian J Med Spec [serial online] 2019 [cited 2021 Feb 28];10:222-4. Available from: http://www.ijms.in/text.asp?2019/10/4/222/270427
| Introduction|| |
Neuromyelitis optica spectrum disorder (NMOSD), as the name suggests, is now a spectrum of disorder encompassing a wide range of involvement such as optic neuritis, myelitis, brainstem lesions, diencephalic lesions, cerebral lesions, and area postrema syndrome (APS). Still, a lot of ground needs to be covered in disseminating the knowledge regarding the lesser known variant of APS subset of NMOSD among health-care professionals. To the best of our knowledge, this is the first case report of APS subset of NMOSD from India.
| Case Report|| |
A 21-year-old female from Bihar, India, was admitted in August 2019 for intractable hiccups, nausea, and intermittent vomiting of around 6 weeks' duration with no apparent response to anti-emetics. Multiple consultations with physicians, gastroenterologists, and a psychiatrist at her home place did not bring any symptomatic relief. On the 2nd week of her illness, while still in her hometown, routine blood tests including liver function tests, serum amylase, lipase, upper gastrointestinal endoscopy, and ultrasonography abdomen were normal. At the start of the 6th week of illness, she started having gait ataxia with giddiness along with multiple episodes of intermittent twisting movements of the right upper limb lasting few seconds. Subsequently, she started having neck drop and swallowing difficulty. Few hours prior to admission at our center, the patient had one episode of generalized tonic-clonic seizure. The patient was immediately intubated and needed mechanical ventilatory support in the intensive care unit. Initial neurological examination revealed normal sensorium, bilateral gaze-evoked nystagmus, poor cough and gag reflex, neck and truncal weakness, right ataxic hemiparesis, and left-sided ataxia. Deep tendon reflexes were brisk in all the four limbs with bilateral extensor plantar response. Further examination also revealed right hemibody hypoesthesia. She never had fever, headache, joint pain, sicca symptoms, orogenital ulcers, cough, or any other significant history. Contrast-enhanced magnetic resonance imaging (MRI) showed a hyperintense signal in the medulla extending into the cervicomedullary junction and upper part of the cervical cord till the second cervical vertebral level in the fluid-attenuated inversion recovery and T2-weighted and diffusion-weighted sequences, not enhancing with a gadolinium injection [Figure 1], [Figure 2], [Figure 3], [Figure 4]. Normal chest X-ray, a negative human immunodeficiency virus serology, negative antinuclear antigen, negative vasculitis profile, and normal serum angiotensin-converting enzyme levels completed the list of investigations. Cerebrospinal fluid (CSF) examination had 60 cells/dl with 100% lymphocytes, protein of 55 mg/dl, and glucose of 122 mg/dl. CSF adenosine deaminase levels were within normal range. CSF Gram stain, India ink stain, and acid-fast bacilli stain were unremarkable. CSF neurovirus panel and autoimmune encephalitis panel also returned negative. Oligoclonal band was not detected in CSF. Electroencephalography done on the 2nd day of admission was normal.
|Figure 1: Magnetic resonance imaging brain showing hyperintensity in the dorsal aspect of the medulla (area postrema region) and cervicomedullary junction in axial fluid-attenuated inversion recovery sequences|
Click here to view
|Figure 2: Magnetic resonance imaging brain showing variable hyperintensity in the dorsal aspect of the medulla (area postrema region) in axial diffusion-weighted images|
Click here to view
|Figure 3: Magnetic resonance imaging brain showing no contrast uptake in the dorsal aspect of the medulla (area postrema region) and cervicomedullary junction in axial T1-weighted contrast images|
Click here to view
|Figure 4: Magnetic resonance imaging of the cervical spinal cord showing hyperintensity in the dorsal aspect of the medulla (area postrema region) and cervicomedullary junction and cervical cord up to the second vertebral level in sagittal fluid-attenuated inversion recovery sequences|
Click here to view
The patient was empirically started on injectable pantoprazole, ondansetron, and levetiracetam and supportive treatment including extensive physiotherapy. Feeding through nasogastric tube was started from the 2nd day onward. Considering the clinical history and MRI findings, a provisional diagnosis of APS was entertained and injection methylprednisolone (MPS) 1 g daily was initiated along with intravenous immunoglobulin (IVIg). No further episodes of hiccups, vomiting, or seizure were encountered, and partial recovery was noted in the right ataxic hemiparesis and left hemiataxia. In view of poor bulbar function, tracheostomy was performed on the 5th day of admission and subsequently, the patient was weaned off the ventilator by the 6th day of admission. After completing 5 days of MPS and IVIg (cumulative dose of 100 g over 5 days administered), tablet prednisolone 50 mg once daily was started. Serum anti-aquaporin-4 IgG antibody (by immunofluorescence assay method) returned positive, and antimyelin oligodendrocyte glycoprotein was negative. On the 11th day of illness, the patient complained of intense itching on the forehead which improved with levocetrizine. The patient subsequently received injection rituximab (cumulative 2 g) at 2 weeks' interval, and tablet mycophenolate mofetil (MMF) (1 g daily) was initiated. The patient is currently recovering well and is able to sit and walk unassisted. Tracheostomy tube and the nasogastric tube were removed on the 13th day of admission in view of remarkable improvement of bulbar function. The patient was discharged home after 36 days of hospital stay in a stable condition with advice for regular follow-up. It has been planned to administer injection rituximab after 6 months with gradual taper down of prednisolone over another 3–4 months and continue MMF.
| Discussion|| |
Since the initial description of NMO in the 19th century, the spectrum of NMO has widened, and it has been renamed as NMOSD.,, This case highlights the less commonly encountered APS subset of NMOSD. Our patient undoubtedly fulfilled the clinico-radiological-immunological diagnostic criteria of NMOSD. There is a lack of awareness of this particular subset of NMOSD among health-care professionals. A large international study published in 2018 revealed that among aquaporin 4-seropositive NMOSD, myelitis was the initial manifestation in 48%, optic neuritis in 42%, APS in 10%, brainstem/diencephalic/cerebral symptoms in 14%, and simultaneous optic neuritis and myelitis in 4% of patients. With the low prevalence rate of 2.6/100,000 of NMOSD in India, the number of APS cases is obviously expected to be few and far in between. The diagnosis in our case was initially elusive prior to presenting to our center, resulting in the delay of initiation of the treatment. In a multicentric, international collaborative study by Shosha et al., 44 out of 100 patients of APS initially presented to a gastroenterologist and none of the patients responded to anti-emetic therapy while they showed rapid and good response to immunotherapy in most of the cases. By the time the patient presented to our center, the patient had accumulated significant neurological deficits. The water channel protein AQP4, the target antigen of NMO-IgG, is preferentially and heavily concentrated in spinal cord gray matter, periaqueductal area, periventricular regions, and astrocytic foot processes at the blood–brain barrier, thereby highlighting the preferential involvement of the above-mentioned areas in NMOSD., Differentials of the area postrema and cervical cord lesions are sarcoidosis, lymphoma, paraneoplastic myelitis, and dural arteriovenous fistula. To the best of our knowledge, this is the first case report of APS subset of NMOSD from India. Our case highlights few points: (a) the lack of awareness regarding APS among health-care professionals, (b) high index of suspicion is paramount for early diagnosis and swift initiation of treatment in APS, (c) area postrema lesions on MRI occurring in association with vomiting or hiccups are characteristic for NMOSD.
| Conclusion|| |
Spreading awareness regarding different varieties of NMOSD, especially APS, should be stressed upon firmly and effectively, thereby aiding in the swift diagnosis and early initiation of therapy in such cases.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published, and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
The authors wish to thank Dr. Sudhir Joseph, Director, St. Stephen's Hospital, Tis Hazari, Delhi, India.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jarius S, Wildemann B. On the contribution of Thomas Clifford Allbutt, F.R.S. to the early history of neuromyelitis optica. J Neurol 2013;260:100-4.
Devic E. Myelite subaigue compliquee de neuriteoptique. Bull Med 1894;8:1033-4.
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.
Kim SH, Mealy MA, Levy M, Schmidt F, Ruprecht K, Paul F, et al.
Racial differences in neuromyelitis Optica Spectrum disorder. Neurology 2018;91:e2089-99.
Pandit L, Kundapur R. Prevalence and patterns of demyelinating central nervous system disorders in urban Mangalore, South India. Mult Scler 2014;20:1651-3.
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.
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.
Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P, et al.
Molecular characterization of an aquaporin cDNA from brain: Candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A 1994;91:13052-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]