Nonalcoholic Wernicke's Encephalopathy Followed by Neuromyelitis Optica Spectrum Disorders: A Case Report
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.273629
Source of Support: None, Conflict of Interest: None
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.
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.
A comprehensive examination of the clinical manifestations resulted in a diagnosis of NMOSD. 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  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. 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, 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. 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.
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. Unlike other CNS autoimmune diseases, it is worth noting that NMOSD lacks intrathecal antibody synthesis. 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. 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.
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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.
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There are no conflicts of interest.
[Figure 1], [Figure 2]