Wernicke’s encephalopathy is a potentially fatal neu-rologic disorder that is caused by a nutritional deficien-cy of thiamine. This malady is characterized by a classictriad of clinical symptoms that include gait ataxia, oph-thalmoplegia and changes in consciousness. Theanatomical sites that are most frequently involved inWernicke’s encephalopathy are the mamillary bodies,periaqueductal regions, bilateral medial thalami, thirdventricular walls, pons, and medulla (1). Wernicke’s en-cephalopathy has been mainly observed in chronic alco-holics, but it may also be associated with other condi-tions that prevent adequate amounts of thiamine frombeing ingested or absorbed. These conditions include

protracted parenteral therapy, gastrointestinal disorders,hyperemesis gravidarum and hunger strike (2). To ourknowledge, the reports that have described the MRimaging features, including the diffusion-weightedimaging changes, of acute Wernicke’s encephalopathyin nonalcoholic patients are very limited. Here, we pre-sent a case of acute Wernicke’s encephalopathy in a pa-tient who had received total parenteral nutrition for hispseudomembranous colitis. The MR imaging, includingthe diffusion-weighted imaging, was performed at theonset and during follow-up. The initial and follow-upMR imaging findings with the diffusion-weighted imag-ing changes are described and correlated with the clini-cal status.

Case Report

A 69-year-old man was referred to the neurology de-partment because of his altered mental status. The pa-tient had been hospitalized for schizophrenia at another

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Diffusion-Weighted MR Imaging in Acute Wernicke’sEncephalopathy Associated with Pseudomembranous

Colitis: A Case Report and Review of the Literature1

Hyeon Yu, M.D., Yong Chul Lee, M.D., Tai Hwan Park, M.D.2, Seung Min Yoo, M.D., Hwa Yeon Lee, M.D., In Sup Song, M.D., Jong Beum Lee, M.D., Kun Sang Kim, M.D.

1Department of Radiology, Chung-Ang University Medical Center2Department of Neurology, Chung-Ang University Medical CenterReceived January 8, 2006 ; Accepted March 29, 2006Address reprint requests to : Hyeon Yu, M.D., Department of Radiology,Chung-Ang University Medical Center, 224-1, Heukseok-dong, Dongjak-gu, Seoul 156-755, Korea.Tel. 82-2-6299-2646-7 Fax. 82-2-6298-8351E-mail: hyeonyu@cau.ac.kr

Wernicke’s encephalopathy is a common complication of thiamine deficiencyamong chronic alcoholics. However, there have been few reports about MR imagingfindings, including the diffusion-weighted changes of this neurologic disorder, in non-alcoholic patients. We present here a rare case of acute Wernicke’s encephalopathythat developed in a patient who received prolonged total parenteral nutrition for hispseudomembranous colitis. The MR imaging, including the diffusion-weighted imag-ing, was performed at the onset of disease and during follow-up. The diagnosis wasmade by the characteristic MR imaging findings and it was supported by the clinicalfeatures. The initial and follow-up MR imaging findings with diffusion-weighted imag-ing changes are described and correlated with the clinical status.

Index words : Brain, diseasesMagnetic resonance (MR) imagingMagnetic resonance (MR) diffusion study

hospital for two years, during which time he had beentreated with risperidone. He had been in his usual stateof health until two months earlier, when a sudden onsetof repeated diarrhea had developed. He was treatedwith antibiotics at that time but the diarrhea continued.A colonoscopic examination was performed by a gas-troenterologist and a diagnosis of pseudomembranouscolitis was made. The patient had been receiving par-enteral nutrition through the central venous catheter to-gether with oral metronidazole. After four weeks, thepatient was transferred to an intensive care unit in thishospital for acute renal failure. The follow-up colono-scopic examination performed at this hospital revealedimprovement of the pseudomembranous colitis. Aboutthree days after transferring, the patient suddenly be-came stuporous.

He had no history of abdominal surgery, hema-tochezia, melena or any contact with ill persons. Hesmoked cigarettes, but he did not drink alcohol. On theneurologic examination, he did not open both eyes topainful stimuli, but grimaced symmetrically. There wasa limitation on the extraocular muscle movement on thehorizontal plane as assessed by the Doll’s eye maneu-ver; however, the pupillary response to the light and thefundoscopic findings were normal. The motor powerswere symmetrically reduced to MRC (Medical ResearchCouncil) grade 2, but there were no involuntary move-ments. The deep tendon reflexes were normoactive, andthe toe signs showed bilaterally flexing. Any signs ofmeningeal irritation were absent.

The laboratory findings including the complete bloodcount, blood chemistry and urine analysis showed nosignificant abnormality except for mild anemia andslightly elevated liver enzymes. Computed tomographyof the brain was performed and it showed no abnormali-ty.

The initial brain MR imaging was performed with a 3-T Achieva system (Philips Medical Systems, Best, TheNetherlands), and it showed symmetrical hyperintenseabnormalities in the medial thalami, periaqueductalgray matter, tectum of the midbrain and the tegmentumof the lower pons and medulla oblongata on the T2-weighted, FLAIR and diffusion weighted images. Thequantitative apparent diffusion coefficient (ADC) mapsshowed decreased ADC values within the bilateral me-dial thalami. Although it was difficult to differentiatethose affected regions from the surrounding unaffectedregions on visual assessment, there were significant dif-ferences in measured signal intensities in those two re-

gions on the ADC map (p < 0.001). Statistical analysiswas performed with a commercially available statisticalsoftware program (SigmaStat 3.11, Richmond,California). A paired sample t test was used to deter-mine the statistical significance of the differences be-tween the lesions and the unaffected areas. The mamil-lary bodies appeared normal in size and they had nor-mal signal intensity. Those affected regions in the brainshowed hypointense signals on the T1-weighted images.The periaqueductal regions, tectum of the midbrain andthe floor of the fourth ventricle showed slight enhance-ment on the contrast-enhanced T1-weighted images. Onthe basis of these MR imaging findings along with hisclinical features, a diagnosis of Wernicke’s encephalopa-thy was made.

The patient began receiving treatment with intra-venous thiamine as soon as the diagnosis was made andthere was steady improvement of his neurologic status.He soon opened his eyes to sound stimuli and recoveredfrom the limitation of eye movements.

About two months after starting intravenous thi-amine, he became alert, fully oriented and was able toconverse. The follow-up MR imaging was performed; itshowed that the previous hyperintensities in the medialthalami, periaqueductal gray matter, tectum of the mid-brain and tegmentum of the lower pons and medulla ob-longata seen on T2-weighted and diffusion weighted im-ages had disappeared. On the FLAIR images, a weak hy-perintense signal was seen in the tectum of the midbrainand the tegmentum of the pons and medulla oblongata.As compared with the initial MR imaging, the third ven-tricle was slightly enlarged, but the mamillary bodiesshowed a normal appearance.

Discussion

Wernicke’s encephalopathy is a potentially fatal neu-rologic disorder that is caused by a thiamine nutritionaldeficiency. In developed countries, Wernicke’s en-cephalopathy has been observed in as many as onefourth of the chronic alcoholics admitted to the generalhospitals (3). However, this disorder may also be associ-ated with other conditions that preclude thiamine frombeing ingested or absorbed in adequate amounts. Theseclinical conditions include hyperemesis gravidarum,protracted parenteral therapy, gastrointestinal disorders,hunger strike and various debilitating illnesses that im-pair the appetite, predispose the patient to vomiting orcause protracted diarrhea. In addition, patients with eat-

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ing disorders, thyrotoxicosis, severe malnourishment orberiberi are also at high risk for contracting Wernicke’sencephalopathy. Most nonalcoholic patients who con-tract Wernicke’s encephalopathy experience only a sin-gle and relatively short period of thiamine deficiency (2,3). Our case was an acute case of Wernicke’s en-cephalopathy that developed in a patient who had beensuffering from continuous diarrhea due to pseudomem-branous colitis for which he had received prolonged to-tal parenteral nutrition without adequate replacement ofthiamine.

Wernicke’s encephalopathy is characterized by a clas-sic triad of symptoms that consist of gait ataxia, ophthal-moplegia and changes in consciousness. In many cases,however, the clinical presentation is not complete andonly changes in consciousness are present (4). The com-

plete clinical triad of Wernicke’s encephalopathy is pre-sent in only 16% of cases. Thus, many cases are misdi-agnosed during patients’ life time, as has been reportedby Harper et al (5). Furthermore, when the patient is ina stuporous or comatose state, which makes neurologicexamination difficult, the clinical diagnosis ofWernicke’s encephalopathy cannot be promptly made.So, in cases that do not present the classical clinical pic-ture, MR imaging is the most important tool for the diag-nosis and instituting timely treatment for acuteWernicke’s encephalopathy (4). In our case, the initialdiagnosis of Wernicke’s encephalopathy was made onthe basis of the characteristic MR imaging findings. Hisclinical history of prolonged total parenteral nutritionfor treating pseudomembranous colitis and the neuro-logic findings of ophthalmoplegia with mental distur-

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A B C

D E FFig. 1. Acute Wernicke’s encephalopathy in a 69-year-old nonalcoholic male patient with pseudomembranous colitis.A-D. Axial FLAIR images demonstrate abnormal hyperintensities in the bilateral medial thalami (arrowheads), periaqueductalgray matter (small solid arrows), tegmentum of the pons and medulla (open arrows), and the bilateral facial nuclei (solid arrows).E. Diffusion-weighted image demonstrates symmetrical hyperintense lesions in the bilateral medial thalami.F. The ADC map demonstrates subtle hypointensities within the bilateral medial thalami.

bance made the possibility of Wernicke’s encephalopa-thy more likely. The patient’s immediate clinical re-sponse to the thiamine treatment was consistent withthe diagnosis.

MR imaging has been considered the most valuabletool not only for the diagnosis of acute Wernicke’s en-cephalopathy, but also for the evaluation of the patho-logic evolution and prognosis of the disorder. Several re-ports and studies on Wernicke’s encephalopathy havedescribed the typical MR imaging features, i.e., symmet-ric hyperintense signal abnormalities in the periventric-ular regions of the dorsomedial thalamus, the hypothal-amus, mamillary bodies, periaqueductal regions, thefloor of the fourth ventricle and the midline cerebellumon the T2-weighted and FLAIR images (4, 6).

The exact pathophysiologic mechanisms that underliethe brain lesions in Wernicke’s encephalopathy are notcompletely understood. Thiamine is a water-soluble es-sential vitamin obtained from the diet. When thiamineis absorbed from the gut, it is phosphorylated to producethiamine pyrophosphate, which is a functionally activecoenzyme form of the vitamin. As a coenzyme, thi-amine has three major functions; these are the oxidativedecarboxylation of α-keto acids, leading to the synthesisof adenosine triphosphate in the pentose phosphatepathway, and maintaining of neural membrane and nor-mal nerve conduction (3). Thiamine deficiency leads toimpaired cerebral energy metabolism, focal lactic acido-sis, N-methyl-D-aspartate receptor-mediated excitotoxi-city, blood-brain-barrier breakdown and decreased os-motic gradients across cell membranes (7). Donnal et al

(6) have documented that the histopathology at the af-fected sites ranged from nearly complete tissue necrosisto the presence of reactive glial cells and mild neuronaland myelin destruction. In most of the minimally dis-eased foci, only proliferation of astrocytes and theprominence of blood vessels were observed, with intactneurons and myelin.

The most frequently involved brain structures inWernicke’s encephalopathy are the periventricular re-gions, the medial formation of the thalamus, the massaintermedia, the floor of the third ventricle and themamillary bodies. Victor et al (1) have reported that themost common gross pathologic lesions were mamillarybody atrophy, vermian atrophy and cerebellar atrophyin his extensive studies of Wernicke-Korsakoff syn-dromes. Microscopic lesions were found in all themamillary bodies and most of the thalami, in which thedorsal medial nuclei were mainly affected. The otherbrain regions that are affected by Wernicke’s en-cephalopathy include the periaqueductal region at thelevel of the third cranial nerve nuclei, the reticular for-mation of the midbrain and the posterior corporaquadrigemina (8).

In our case, most of the involved regions in the brainwere the typical ones and they were the bilateral medialthalami, the periaqueductal gray matter, the tectum ofthe midbrain and the tegmentum of the lower pons andmedulla oblongata. These structures were hyperintenseon the T2-weighted and FLAIR images. Among thosetwo MR imaging sequences, the FLAIR images demon-strated the affected regions more clearly than did the

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A B CFig. 2. Follow-up MR imaging performed at approximately two months after starting thiamine treatment. The axial FLAIR image(A) and diffusion-weighted images (B) demonstrate complete resolution of the previously noted areas of hyperintense signal abnor-malities in the bilateral medial thalami. The third ventricle shows slight dilatation compared with the initial MR imaging. The axialT1-weighted inversion recovery image (C) demonstrates the normal appearance of the bilateral mamillary bodies (arrows).

T2-weighted images; this is presumably due to MRI’sability to suppress the adjacent cerebrospinal fluid sig-nal intensity that might mask high signal lesions on theT2-weighted images. The affected regions were hy-pointense on the T1-weighted images. Those affected re-gions, except the bilateral medial thalami, showed mildenhancement on the contrast-enhanced T1-weightedimages. The explanation of this contrast enhancement isprobably related to breakdown of the blood-brain barri-er, which is one of the relatively early histopathologicchanges (7).

There have been a few reports that described atypicalMR imaging findings of Wernicke’s encephalopathy.Bae et al (9) reported a case with atypical regions in thebrain that were involved in Wernicke’s encephalopathy,and this was accompanied by bacterial meningitis andbrain abscess. MR imaging demonstrated symmetric hy-perintense signal abnormalities in the bilateral cerebel-lar dentate nuclei and red nuclei, in addition to injuriesof the tegmentum of the lower pons, bilateral facial nu-clei and bilateral vestibular nuclei on the T2-weightedand FLAIR images. In our case, we have found atypicallesions in the bilateral facial nuclei and the tegmentumof the lower pons that were hyperintense on the T2-weighted and FLAIR images.

Diffusion-weighted imaging of our patient with acuteWernicke’s encephalopathy demonstrated hyperintensesignal abnormalities within the regions corresponding tothe areas of increased signal intensities on the T2-weighted and FLAIR images. Among those affected re-gions, the bilateral medial thalami showed the brightestsignal intensity. On the ADC map images, only the bilat-eral medial thalami showed decreased values of the dif-fusion coefficients; this is consistent with restricted dif-fusion and cytotoxic edema. The other affected regionsshowed an increase in the values of the diffusion coeffi-cients on the ADC maps; this is consistent with the T2-shine-through effect. Halavaara et al (10) have reportedthat all of their patients with Wernicke’s encephalopa-thy demonstrated increased intensity of the diffusion-weighted imaging signal and increased ADC values inthe bilateral medial thalami, except for one patient whodemonstrated decreased ADC values in the same re-gions. They suggested that both cytotoxic and vasogenicedema contributed to the findings observed on diffu-sion-weighted images and the ADC maps. Althoughhigh signal intensity on the diffusion-weighted imagesand the decreased ADC values in acute Wernicke’s en-cephalopathy are associated with cytotoxic edema, it

does not always correspond to irreversible tissue dam-age (2). Follow-up MR imaging of our case that was ob-tained two months later showed the absence of the iden-tified signal abnormalities in all the affected areas on theT2-weighted and diffusion-weighted images, althoughsome slight hyperintense signal abnormalities weredemonstrated in the periaqueductal region, the floor ofthe fourth ventricle and the tegmentum of the medullaon the FLAIR images. Several studies have shown thatwhen thiamine is replenished in adequate amounts, thesignal abnormalities may normalize within 14 days andthis represents reversible cytotoxic edema before the on-set of necrosis (2).

Zhong et al (7) reported that the lesions of the bilateralmedial thalami were related to the degree of mental dis-turbance in acute Wernicke’s encephalopathy patients.They have found that the patients without coma exhibit-ed only periaqueductal lesions, but all the patients withcoma presented with the lesions of the bilateral medialthalami and the head of the caudate nuclei in the acutephase of nonalcoholic Wernicke’s encephalopathy. Ourcase confirmed this relationship between the degree ofconsciousness disturbance and the damage of the bilat-eral medial thalami observed on MR imaging in theacute phase of nonalcoholic Wernicke’s encephalopa-thy.

It has been reported that the most common pathologiclesions in Wernicke’s encephalopathy are mamillarybody atrophy, vermian atrophy and cerebellar atrophy(1). However, a few studies have shown that there is adifference on the MR imaging findings of Wernicke’sencephalopathy between alcoholics and the nonalco-holic patients. The difference between the two groupsmaybe due to the fact that the cerebellar vermis andmamillary bodies are susceptible to thiamine deficiencyin alcoholic patients; further, alcoholic patients mighthave had previous attacks of Wernicke’s encephalopa-thy, and the MR imaging findings in the acute phasewere contaminated by previous injury (7). Zhong et al(7) have reported that none of their patients with acutenonalcoholic Wernicke encephalopathy presented withatrophy of the cerebellar vermis and mamillary bodies.Increased signal intensities in the periaqueductal re-gions, the periventricular regions and the medial thala-mi on the T2-weighted and FLAIR images were themain findings. Our case did not show atrophy of thecerebellar vermis and mamillary bodies on MR imagingat the onset of disease and during follow-up. We believethat the MR imaging findings of our case clearly demon-

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strated the pathologic evolution in the first episode ofacute nonalcoholic Wernicke encephalopathy withoutprevious attacks, and it confirmed that the MR imagingfindings of nonalcoholic patients are different fromthose of alcoholics.

In conclusion, we present here a case of acute nonal-coholic Wernicke encephalopathy in which convention-al MR imaging and diffusion-weighted imaging wereperformed at the onset of disease and during follow-up.The signal abnormalities in the brain observed at the ini-tial MR imaging resolved with time and this showed adirect relationship to the clinical symptoms on the fol-low-up examinations. In addition, diffusion-weightedimaging was advantageous in depicting bilateral medialthalamic lesions and it could be helpful for diagnosingWernicke’s encephalopathy and assessing the patient’sprognosis.

References

1. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff syn-drome: a clinical and pathologic study of 245 patients, 82 withpost-mortem examination. Contemp Neurol Ser 1971;7:1-206

2. Unlu E, Cakir B, Asil T. MRI findings of Wernicke encephalopa-thy revisited due to hunger strike. Eur J Radiol 2006;57:43-53

3. Kane AB, Kumar V. Environmental and Nutritional Pathology:Nutrition and Disease. In Kumar V, Abbas AK, Fausto N. Robbinsand Cotran Pathologic Basis of Disease. 7th ed. Philadelphia:Elsevier Saunders, 2005:456-457

4. Victor M. MR in the diagnosis of Wernicke-Korsakoff syndrome.AJR Am J Roentgenol 1990;155:1315-1316

5. Harper CG, Giles M, Finlay-Jones R. Clinical signs in theWernicke-Korsakoff complex: a retrospective analysis of 131 casesdiagnosed at necropsy. J Neurol Neurosurg Psychiatry 1986;49:341-345

6. Donnal JF, Heinz ER, Burger PC. MR of reversible thalamic le-sions in Wernicke syndrome. AJNR Am J Neuroradiol 1990;11:893-894

7. Zhong C, Jin L, Fei G. MR imaging of nonalcoholic wernicke en-cephalopathy: a follow-up study. AJNR Am J Neuroradiol 2005;26:2301-2305

8. Yokote K, Miyagi K, Kuzuhara S, Yamanouchi H, Yamada H.Wernicke encephalopathy: follow-up study by CT and MR. JComput Assist Tomogr 1991;5:835-838

9. Bae SJ, Lee HK, Lee JH, Choi CG, Suh DC. Wernicke’sEncephalopathy: atypical manifestation at MR imaging. AJNR AmJ Neuroradiol 2001;22:1480-1482

10. Halavaara J, Brander A, Lyytinen J, Setala K, Kallela M.Wernicke’s encephalopathy: is diffusion-weighted MRI useful-Neuroradiology 2003;45:519-523

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대한영상의학회지 2006;54:453-458

거짓막대장염에 동반된 급성 베르니케 뇌병증의 확산강조자기공명영상 소견: 증례보고 및 문헌고찰1

1중앙대학교 의료원 영상의학과2중앙대학교 의료원 신경과

유 현·이용철·박태환2·유승민·이화연·송인섭·이종범·김건상

베르니케 뇌병증은 만성 알코올중독자들에게서 티아민이 부족할 때 흔히 발생하는 합병증이다. 하지만, 알코올중

독자가 아닌 일반 환자들에게서 발생한 베르니케 뇌병증의 확산강조영상을 포함한 자기공명영상 소견에 관해서는 그

보고가 많지 않다. 최근 저자들은 거짓막대장염으로 인해 장기간 전비경구적 영양공급을 받은 비알코올성 환자에게

서 급성 베르니케 뇌병증이 발생했던 증례를 경험하였기에 이를 보고하고자 한다. 급성 뇌병증이 발생했을 당시와 후

에 임상적 경과가 호전되었을 때 확산강조영상을 포함한 뇌자기공명영상 검사를 시행했다. 임상적 증상들과 더불어

자기공명영상에서 보였던 특징적인 방사선학적 소견을 근거로 베르니케 뇌병증을 진단할 수 있었다. 본 저자들은 확

산강조영상을 포함한 뇌 자기공명영상의 특징적 소견과 변화를 기술하였으며 환자의 임상적인 경과와도 비교하였다.