Atormac
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 1382  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (1,076 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this Article
   References
   Article Figures

 Article Access Statistics
    Viewed235    
    Printed4    
    Emailed0    
    PDF Downloaded7    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
LETTER TO EDITOR
Year : 2019  |  Volume : 67  |  Issue : 6  |  Page : 1562-1564

Nonalcoholic Wernicke's Encephalopathy Followed by Neuromyelitis Optica Spectrum Disorders: A Case Report


Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, P. R. China

Date of Web Publication20-Dec-2019

Correspondence Address:
Dr. Ganqin Du
No. 24 Jinghua Road, Yuxi District, Luoyang, Henan Province Henan Province, 471003; Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003
P. R. China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.273629

Rights and Permissions



How to cite this article:
Zhang D, Yang X, Zhang Z, Zhao W, Duan P, Du G. Nonalcoholic Wernicke's Encephalopathy Followed by Neuromyelitis Optica Spectrum Disorders: A Case Report. Neurol India 2019;67:1562-4

How to cite this URL:
Zhang D, Yang X, Zhang Z, Zhao W, Duan P, Du G. Nonalcoholic Wernicke's Encephalopathy Followed by Neuromyelitis Optica Spectrum Disorders: A Case Report. Neurol India [serial online] 2019 [cited 2020 Jan 26];67:1562-4. Available from: http://www.neurologyindia.com/text.asp?2019/67/6/1562/273629




Sir,

Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory disorders of the central nervous system (CNS) characterized by episodes of immune-mediated demyelination. Wernicke's encephalopathy (WE) is a neurological disorder which occurs due to thiamine (Vitamin B1) deficiency. WE and NMOSD are completely different disease entities. We report here the first case of a 28-year-old woman presenting WE with subsequent NMOSD. Are there any potential correlations between these two diseases?

A 28-year-old woman was transferred to our hospital with diplopia and unstable walking. During the one month period prior to admission, she experienced intermittent vomiting, nausea, reduced food intake and unintentional weight loss. Four days before admission, she showed a gradual increase in diplopia and unstable walking. She had always been in good health and had no history of alcohol use.

The general physical examination on admission was normal except for a white patch of depigmentation on the neck. Neurological examination showed left abducens nerve palsy and bilateral gaze-evoked nystagmus. She also demonstrated inaccurate nose touch test, inaccurate heel-knee-tibia test and positive Romberg's sign. She was unable to walk in a straight line. The remainder of the neurological examination was normal.

After admission, routine clinical laboratory tests were unremarkable, except for a platelet count of 50 * 109/L. Blood biochemical tests showed no abnormalities. An extensive autoimmune workup was performed, and the results were positive for Ro/SSA (60 Kd). Cerebrum magnetic resonance imaging (MRI) images showed hyperintense lesions around the fourth ventricle [Figure 1]a, the periaqueductal area [Figure 1]b and the third ventricle [Figure 1]c and [Figure 1]d.
Figure 1: Axial fluid-attenuated inversion-recovery (FLAIR) images shows hyperintense lesions (white arrows) around the fourth ventricle (a), the periaqueductal area (b), and the third ventricle (c and d). Review FLAIR images shows the previous lesion around the fourth ventricle (e), the periaqueductal area (f), and the third ventricle (g and h) disappeared

Click here to view


She was diagnosed with non-alcoholic WE. We performed replacement therapy with thiamine. Two weeks after the initiation of high-dose thiamine treatment, her eye movements were normal and the ataxia improved. She was discharged 21 days after admission. At her follow-up visit approximately 1 month later, brain MRI FLAIR images showed that the previous lesion around the ventricles (the third and fourth ventricles), and the periaqueductal area disappeared [Figure 1]. She had full neurological recovery.

Six months after her last discharge, she was admitted to our hospital due to urinary incontinence and numbness in her limbs and trunk. She stated that the numbness of the lower limbs had started one month prior to her presentation and had gradually progressed to her trunk. She experienced urinary incontinence one week prior to her presentation. One week before admission, she experienced urinary incontinence. She experienced no visual disturbances.

Neurological examination showed dysesthesia below the 4th thoracic dermatome. The radial periosteal reflexes and patellar tendon reflexes were exaggerated. Other neurological examinations were normal.

Routine laboratory and blood biochemical tests revealed no abnormalities. Serum anti-aquaporin 4 (AQP4) antibodies were positive measured by an enzyme-linked immunosorbent assay. However, cerebrospinal fluid (CSF) examination showed no leukocytosis, no oligoclonal bands and no AQP4 antibodies. Autoimmune workup revealed titers of antinuclear antibody (ANA) (S1:320); Ro/SSA (60 Kd), positive; Ro/SSA (52 Kd), positive, complement 3 (C3) 0.88 g/L, complement 4 (C4) 0.12 g/L. T2-weighted MRI images showed swelling of the spinal cord and strip hyperintense from the level of C1 to C8 [Figure 2]a. However, the visual evoked potential was normal.
Figure 2: Axial T2-weighted MRI images showed swelling of the spinal cord and strip hyperintense (white arrows) from the level of C1 to C8 (a). Review axial MRI examination at one year after the onset showed swelling of the spinal cord and strip hyperintense lesion has lightened (b). Axial T2-weighted MRI images of the spinal cord showed hyperintense lesions (white arrows) from the level of C1 to C3 (c). Review axial T2-weighted MRI images of the spinal cord showed hyperintense lesions (white arrows) from the level of C1 to C3 (d)

Click here to view


A comprehensive examination of the clinical manifestations resulted in a diagnosis of NMOSD.[1] The patient accepted methylprednisolone pulse therapy (1 g, 3 days). To prevent attacks, we initiated treatment with azathioprine and tapered the dose of prednisone. Twenty-one days after admission, she felt that the numbness of her trunk and limbs was significantly relieved. The patient was discharged but continued to take immunosuppressive drugs and gradually reduced oral corticosteroids. She had no recurrence at the one year follow-up period under the treatment of immunosuppressive agents. The results of a review MRI examination one year after the onset showed swelling of the spinal cord and the strip hyperintense lesion lightened [Figure 2]b.

Two years after the first NMOSD onset, she relapsed with symptoms of numbness of head and face. Lhermitte's phenomenon was found to be positive by neurological examination. AQP4 antibodies were positive not only in serum and but also in cerebrospinal fluid. Spinal cord T2-weighted MRI images of the spinal cord showed hyperintense lesions from the level of C1 to C3 [Figure 2]c. She received steroid pulse therapy, and her condition had not progressed. She continued to take immunosuppressive therapy after discharge. Three months after the relapse, she was in good condition except for a slight numbness on the left side of her face. A careful review MRI examination showed no significant improvement in the original lesions [Figure 2]d.

The patient presented with two distinct diseases sequentially: nonalcoholic Wernicke encephalopathy and neuromyelitis optica spectrum disorders. Our patient was diagnosed with non-alcoholic WE [2] as she had the typical eye signs, ataxia and lesions around the ventricles (the 3rd and 4th ventricles) and the periaqueductal area. The efficacy of adequate thiamine therapy further proved the diagnosis. She was diagnosed with NMOSD because her serum anti-AQP4 antibody was positive and the transverse long segment spinal cord lesions were typical of NMOSD. To our knowledge, our patient is the first case with non-alcoholic WE followed by seropositive NMOSD.

Wernicke's encephalopathy is a classic neurological disorder which occurs due to thiamine deficiency (TD). The impaired oxidative metabolism in TD results in major changes in cerebral function that include lactic acidosis, cytotoxic edema, and blood-brain barrier (BBB) dysfunction.[3] TD influences both neurons and astrocytes of the cerebrum. Recent studies have demonstrated that astrocytes are a major source of lactate production in the brain,[4] with increased lactic acidosis in TD. Furthermore, previous findings indicate that TD leads to the swelling of astrocytes in association with altered levels of AQP4, a major water channel protein that is localized in astrocytes in brain.[5] Because swelling is a significant characteristic of TD, astrocytes may be a key player in the observed brain edema in WE. In addition, astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Thus, TD causes BBB breakage by targeting astrocytes, which leads to dysregulation in the movement of ions, molecules and cells between the neural cells and the blood in the CNS. Thus, these abnormalities further cause disorder of ionic homeostasis, hormone and transmitter levels and transport of nutrients in the brain.[6]

NMOSD is characterized by astrocytic damage and demyelination caused by AQP4-IgG attack. AQP4 is particularly prevalent in astrocytic membranes at the blood-brain and brain-liquor interfaces. NMOSD is a disabling autoimmune astrocytopathy. Pathology studies have found that astrocytes are selectively targeted in NMOSD.[7] Unlike other CNS autoimmune diseases, it is worth noting that NMOSD lacks intrathecal antibody synthesis.[8] Serum AQP4-IgG might be present for years before the onset of NMOSD. Perhaps an additional factor transiently disrupts the integrity of the BBB, especially in the spinal cord or optic nerve, allowing AQP4-IgG access. TD may be one such factor.

In the CNS, astrocytes have been shown to express most metabolic enzymes, induce inflammation and form glial scars. Thus, they may be responsible for many of the neurological symptoms observed in metabolic disorders and play a significant role in the demyelinating disease progression as glial scars hinder remyelination. In the pathophysiology of both TD and WE, astrocyte targeting leads to lactic acidosis, BBB breakdown and AQP4 changes.[3] Although the major initiator of WE is the impaired oxidative metabolism and the changes in cerebral function mediated by astrocytes, TD and immune-mediated neurological disorders somehow exacerbate each other.

There are correlations between NMOSD and WE. Astrocytes may play a significant role in the pathophysiology of both of these diseases.

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 Top

1.
Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology 2015;85:177-89.  Back to cited text no. 1
    
2.
Galvin R, Bråthen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA; EFNS. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy[J]. Eur J Neurol 2010;17:1408-18.  Back to cited text no. 2
    
3.
Abdou E, Hazell AS. Thiamine deficiency: An update of pathophysiologic mechanisms and future therapeutic considerations [J]. Neurochem Res 2015;40:353-61.  Back to cited text no. 3
    
4.
Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, et al. Activity-dependent regulation of energy metabolism by astrocytes: An update[J]. Glia 2007;55:1251-62.  Back to cited text no. 4
    
5.
Chan H, Butterworth RF, Hazell AS. Primary cultures of rat astrocytes respond to thiamine deficiency-induced swelling by downregulating aquaporin-4 levels[J]. Neurosci Lett 2004;366:231-4.  Back to cited text no. 5
    
6.
Luissint AC, Artus C, Glacial F, Ganeshamoorthy K, Couraud PO. Tight junctions at the blood brain barrier: Physiological architecture and disease-associated dysregulation[J]. Fluids Barriers CNS 2012;9:23.  Back to cited text no. 6
    
7.
Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: Lessons learned from neuromyelitis optica[J]. Brain Pathol 2014;24:83-97.  Back to cited text no. 7
    
8.
Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: Results from 211 lumbar punctures[J]. J Neurol Sci 2011;306:82-90.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow