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Radiology of Infectious Diseases 3 (2016) 79e83

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Case report

Neuromyelitis optica and Wernicke encephalopathy share the similarimagings, any correlations?

Jing Yang a, Dajiang Wang b, Jichen Wang d,1, Yu Chen a, Xin Lou c, Boyan Fang a,*a Department of Neurology, Aerospace Center Hospital, 15th Yuquan Road, Beijing, 100049, China

b Department of Ophthalmology, Chinese PLA General Hospital, 28th Fuxing Road, Beijing 100853, Chinac Radiology, Chinese PLA General Hospital, 28th Fuxing Road, Beijing 100853, China

d Yong Ding Road Middle School of Beijing, 13th Jingou He Road, Beijing 110000, China

Received 5 March 2016; revised 22 March 2016; accepted 23 March 2016

Available online 30 March 2016

Abstract

Two cases with similar brain imaging findings were reported. Both brain MRIs were characterized by abnormal signal intensities in thalamus,surrounding third ventricle, periaqueductal areas and posteromedial thalami. Through clinical observation and a series of auxiliary examinations,one patient was diagnosed as Wernicke encephalopathy (WE) and the other as neuromyelitis optica (NMO). Although WE and NMO are totallydifferent diseases entity, but similar lesions area aroused hypothesis that potential correlations may exist between these two diseases. Astrocytesmay be the target cells connecting these two diseases. Potential benefit of thiamine supplementary therapy is suggested for NMO treatment.© 2016 Beijing You’an Hospital affiliated to Capital Medical University. Production and hosting by Elsevier B.V. This is an open access articleunder the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: Wernicke encephalopathy (WE); Neuromyelitis optica(NMO); Imagings; Astrocytes

1. Introduction

Neuromyelitis optica (NMO) and Wernicke encephalopathy(WE) are totally different diseases entity. NMO is an auto-immune disease which NMO-IgG immune response leads todemyelination. The antibodies target aquaporin-4 in the cellmembranes of astrocytes which acts as a channel for thetransport of water across the cell membrane. While WE resultsfrom deficiency of vitamin B1 (thiamine hydrochloride) whichhelps to breakdown glucose. Specifically, it acts as an essentialcoenzyme in the TCA cycle and the pentose phosphate shunt.Human body only has 2e3 weeks of thiamine reserves, whichare readily exhausted without intake, or if depletion occursrapidly, such as in chronic inflammatory states or in diabetes.From a hyperemesis gravidarum patient, unexpectedly we

* Corresponding author. Tel.: þ86 10 59971956; fax: þ86 10 59971955.

E-mail address: fangboyanv@163.com (B. Fang).

Peer review under responsibility of Beijing You'an Hospital affiliated to

Capital Medical University.1 This author is a pre-college student (Yong Ding Road Middle School).

http://dx.doi.org/10.1016/j.jrid.2016.03.004

2352-6211/© 2016 Beijing You’an Hospital affiliated to Capital Medical University

the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

found that the cranial MRIs of these two diseases are quitesimilar. The common lesions would involve thalamus, hypo-thalamus, peri-third ventricle and fourth ventricle, peri-aqueductal, brain stem and cerebellum. Their initialpresentations are easy misdiagnosis, including visual changes,intractable vomiting. Are there any correlations between themtwo?

2. Case report

2.1. Case 1

A 24-year-old woman was admitted for blurred vision for9 h and convulsion for 1 h. Nine hours before admission,blurred vision occurred abruptly and aggravated gradually andlost vision after a dispute with others. Sudden convulsionsoccurred during the patient's consultation. Two times of out-breaks occurred in 2e3 min. The past medical history impliedthe patient now is 3 months pregnant with nausea and vom-iting for more than a month. Physical examination upon

. Production and hosting by Elsevier B.V. This is an open access article under

80 J. Yang et al. / Radiology of Infectious Diseases 3 (2016) 79e83

admission indicated no light perception was found in botheyes. Laboratory examinations showed blood glucose10.7 mmol/L, Kþ3.5 mmol/L, Naþ132 mmol/L, Cl�

9.5 mmol/L; ENA and ANCA spectrum, WidalePei test,syphilis and HIV blood test were all negative. Serum thiaminewas 51 nM/L (normal > 70). Head CT scan revealed suspi-cious flake-like hypoattenuated lesions in the left occipitallobe, and MRI showed slightly longer T1 and T2 signal in-tensities in bilateral occipital cortex, and slightly longer T1and T2-weighted sheeted signal intensities symmetricallydistributed surrounding aqueduct and third ventricle (Fig. 1).Lumbar puncture showed cerebral spinal fluid pressure of100mmH2O, protein 1þ, cells 1þ, sugar 3.4 mmol/L, totalprotein 0.3 g/L, Cl-127 mmol/L, and LDH 64U/L. Acid-resistent bacilli, fungi, and neocryptococcosis in cerebralspinal fluid were all negative. AQP-4 antibody was alsonegative.

Wernicke Encephalopathy was diagnosed. After vitaminB1 supplementing for 5 days, her neurologic examinationshowed a slight recovery of conscious, vision acuity was 1 m/FC (finger counting). 7 days later, visual acuity and visualfield of both eyes were normal. The patient's condition wasrelatively stable, but her emotional expressions were

Fig. 1. Axial FLAIR images showing asymmetric hyperintensities in bilateral occip

periaqueductal areas (E, F).

indifferent and unresponsive. Ten days later, the patient'scondition improved gradually, but with memory impaired.After 20 days continuous treatment, her consciousness andcognitive function were resolved completely. A follow-upcranial MRI scanning 2 weeks later FLAIR showed highpunctiform and banding-shaped signal in left parietal lobeand slightly higher signal intensity in surrounding cerebralaqueduct, the lesion reduced significantly compared to priorexaminations. Laboratory results were normal. Vaginal de-livery was induced after admission into obstetric department.One year after discharge, a telephone call follow-upconfirmed that her blood pressure and visual acuity werenormal and no seizures had reoccurred.

2.2. Case 2

A-21-year-old woman was admitted for complaint ofvertigo and vomiting for 3 days and drowsiness for 1 day.Three days before admission, vertigo occurred abruptly aftermorning rises, accompanied with nausea and obviouslyvomiting. The patient did not have headache, fever, physicalactivity disturbance and limb paresthesia. She was not given adiagnosis and treatment. One day before admission, she was

ital lobe (A, B), surrounding third ventricle and posteromedial thalami (C, D),

81J. Yang et al. / Radiology of Infectious Diseases 3 (2016) 79e83

found being depression and lethargy by her family members.Upper respiratory tract infection occurred 3 days before theonset. Physical examination upon admission indicated alethargy status, no local neurological signs. Head MRIshowed slightly longer T1 and T2 signal intensities in hy-pothalamic region, and a slightly longer and symmetricaldistribution of T1 and T2-weighted sheeted signal intensitiesin the surrounding aqueduct and third, fourth ventricle(Fig. 2AeC). Wernicke Encephalopathy was suspectedinitially.

Two days after admission, the patient complained ofwalking difficultly, weakness, and numbness. New lesionswere observed on the T2 and fluid-attenuated inversion re-covery weighted MRIs of the medulla oblongata and cervical 2level (Fig. 2D). Spinal fluid pressure is 140mmH2O, cells 10

þ,glucose 4.1 mmol/L, total protein 0.46 g/L, Cl� 123 mmol/L.

Fig. 2. Axial T2-weighted image showing hyperintensity (white arrows) in the su

showing abnormal hyperintensity around the third and fourth ventricle (B, C). Sagit

cervical 2 level (D).

AQP-4 antibody test was positive. Neuromyelitis optica wasconsidered. Her condition was improved with pulse prednis-olone (1 g/d). On followed up one year later, she was hospi-talized the second time due to vision loss.

3. Discussion

These two cases showed us two completely different dis-eases, WE and NMO. Case 1 had an atypical presentation ofWernicke's encephalopathy (WE) with cortical blindness.Onset of WE results from deficiency of vitamin B1 (thiaminehydrochloride) which help to breakdown of glucose [1]. Itacts as an essential coenzyme in the TCA cycle and pentosephosphate shuttle [2]. Human body only has 2e3 weeks ofthiamine reserves, which are easily exhausted without intake,or if depletion occurs rapidly, such as in chronic

rrounding aqueduct (A). Coronal fluid-attenuated inversion recovery images

tal T2-weighted image showing abnormal hyperintensity from brainstem to the

82 J. Yang et al. / Radiology of Infectious Diseases 3 (2016) 79e83

inflammatory states or in diabetes. Endothelial swelling in thecapillaries, microglial activation, petechial hemorrhage, andnecrosis are main pathological manifestations [3]. Clinicalpresentations include ophthalmoplegia, ataxia, and confusion[4]. More diverse symptoms such as amblyopia, pupillarychanges, retinal hemorrhage, papilledema, vision and hearingloss, epilepsy, lactic acidosis, memory impairment, psychosis,hypothermia, polyneuropathy, hyperhidrosis have been re-ported. On the late stage, hyperthermia, increased muscletone, spastic paralysis, choreic dyskinesias and coma may bepresented. Symmetrical lesions are usually observed in peri-ventricular region, periaqueductal gray matter and tectum ofthe dorsal mid-brain [5], medial thalamic nuclei, hypothala-mus and cerebellar vermis. Edema may be found in regionssurrounding the third, fourth ventricle. Symptoms arereversible with adequate administration of thiamine. Memorydisorder may remain permanently [6]. Case 2 was consideredNMO. NMO is an autoimmune demyelinating disease, whichis mediated by AQP-4 antibody targeting AQP-4 waterchannel of astrocytes [7,8]. A series of pathological changesoccurred including extensive complement activation, eosin-ophil/neutrophil cells infiltration and vascular fibrosis inearly, active demyelinating NMO lesions [9,10]. Clinicalmanifestations of NMO include vision loss, ophthalmoplegia,limbs paresis, sensory disturbance, or loss of bladder andbowel control, ataxia, etc [11]. Typical abnormalities on brainMRI are usually located at sites with high aquaporin-4expression areas. Lesions could involve optic chiasm, peri-ethird ventricle and fourth ventricle, periaqueductal, post-rema area, thalamus, hypothalamus, and sometimecerebellum, subpial and periependymal, corpus callosum[12]. NMO always results in severe sequel after an acuteepisode [13].

By comparing the clinical symptoms and imaging findingsof two cases, we found many similarities, especially head MRIfindings. Astrocytes may be the key players in the patho-physiology of both NMO and WE [14].

WE is a classic neurological syndrome induced by thiaminedeficiency (TD). During WE, onset of neurological symptomsoccurs when thiamine level falls to less than 15% of normalvalues. Thiamine deficiency affects both neurons and astro-cytes, glial cells of the brain. TD is known to alter astrocyticexpression of glutamate transporters (excitatory amino acidtransporter 1and excitatory amino acid transporter 2, EAAT1and EAAT2), in addition to up regulating inflammatory genesand transcription factors controlling inflammatory genes.Other changes include those to the gamma-aminobutyric acid(GABA) transporter subtype GABA transporter-3 (GAT-3),glial fibrillary acidic protein (GFAP), glutamine synthetase.WE also experience inflammatory process, alter the levels ofaquaporin-4 (AQP-4) [15]. Focal lactic acidosis also causessecondary edema, oxidative stress, inflammation and whitematter damage [16]. Recent studies have also demonstratedthat TD in cultured astrocytes leads to swelling of these cellswhich is associated with alterations of the levels of AQP-4[17]. Thus, lactic acidosis may mediate these changes inAQP-4 expression which lead to swelling of the astrocytes in

TD with pathological consequences. Indeed, recent evidencesupports this contention whereby lactic acid increases AQP-4gene expression in astrocytes [15]. An inflammatory processincluding the early presence of increased microglial reactivity[18], while production of proinflammatory cytokines both invulnerable and non-vulnerable regions of brain have been re-ported [19e21]. Zhe Ji et al. [22] also reported TD mightinfluence the outcome of neuroinflammation by upregulatingin chemokine (CeC motif) ligand 2 (CCL2) and its receptorCCR2 in experimental autoimmune encephalomyelitis.

NMO is an IgG-mediated astrocytopathy, in whichaquaporin-4 is the target of NMO-IgG. When brain lesionsoccur in NMO, they are often located in the midline of thebrain (which is aquaporin-4 enriched), as do lesions of WE.The multiple molecular outcomes identified as a consequenceof NMO-IgG interaction with AQP4 plausibly account for thediverse pathological features of NMO: edema, inflammation,demyelination, and necrosis [23]. The pathogenesis of NMO iscomplex as binding of NMO-IgG to AQP4 in the human CNScan cause direct water blockade, AQP4 internalization withsecondary water blockade, EAAT2 down-regulation andglutamate exictotoxicity, and/or activation of the lytic com-plement cascade with destruction of astrocytes [24].

TD modulates neuroinflammation at the level of theastrocyte. Astrocytes are five times more abundant than neu-rons. Astrocytes are the major regulators of water, ion andglutamate homeostasis, and are the guardians of the bloode-brain barrier. When activated they become professionalantigen-presenting cells, produce numerous cytokines andchemokines and most complement proteins, and form a scar toprevent inflammation spread [14]. We suggest astrocytes as thekey players both in the pathophysiology of NMO and in WE.Although impaired oxidative metabolism is a major initiator ofWE, TD and immune-mediated neurological disorders some-how exacerbate each other. Thiamine as an inexpensive sup-plementary therapeutic strategy for immune-mediatedneurological disorders should be considered [14].

Acknowledgment

Acknowledgement statement (including conflict of interestand funding sources): All authors' declaration of interests. Theauthors thank Bin Cui for preparing imagings. Boyan Fangwas supported by China Scholarship Council Exchange(Scholarship 201203070619).

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