Professional Documents
Culture Documents
Euro J of Neurology - 2010 - Galvin - EFNS Guidelines For Diagnosis Therapy and Prevention of Wernicke Encephalopathy
Euro J of Neurology - 2010 - Galvin - EFNS Guidelines For Diagnosis Therapy and Prevention of Wernicke Encephalopathy
NS, not specified; H, hospital series; CO, Coroner series; WE, Wernicke encephalopathy.
5.7
Findings
33
20
How often is WE diagnosed in life?
No. of diagnosed
Autopsy studies indicate that WE is frequently undi-
ante mortem
agnosed during life. Table 2 lists the autopsy studies
reporting the percentage of alcoholic and non alco-
holic patients with WE diagnosed ante mortem. All
1
1
0
2
Non alcoholics
were Class IV studies. WE was suspected during life in
only about one-third of alcoholic and 6% of non
autopsies
No. of
alcoholic patients. These series are likely to be biased
towards more severe cases and the number of patients
3
5
19
35
remaining undiagnosed before death is probably
higher. These observations would suggest that thia-
100.0
84.9
5.3
19.8
33.3
36.4
21.4
33.3
22.2
31.9
0
mine deficiency and its consequences are likely to
%
remain undiagnosed during life in significant numbers
of cases. We are probably underestimating the real
No. of diagnosed
incidence of the disease and it seems reasonable to
ante mortem
recommend that an autopsy has to be performed when
patients die in situations with a suspicion of thiamine
deficiency.
45
1
26
2
4
0
3
1
4
87
Recommendation
Alcoholics
autopsies
Patients dying from symptoms suggesting WE should No. of
have an autopsy (GPP).
53
19
1
131
11
17
14
3
18
273
When should we suspect WE in non alcoholic subjects?
H
H
H
H
H
H
NS, not specified; H, hospital series; CO, Coroner series. a>90% alcoholics.
included fasting, starvation, malnutrition and the use
of unbalanced diets. Systematic reviews have been
Evidence
IV
IV
IV
Australia, Sydney
Australia, Pertha
Norway
Norway
France
USA
USA
Area
1950–61
1975–79
1973–81
1983–87
1988–89
1983–86
1996–97
1984–99
2001–06
NS
may disappear.
Harper [42,43]
Riethdorf [50]
Ogershok [59]
Bertrand [58]
Recommendation
Lindboe [46]
Harper [56]
Naidoo [49]
Harper [45]
Sheedy [55]
Torvik [41]
Victor [40]
[reference]
Vege [51]
Kuo [60]
Total
bariatric surgery we recommend follow-up of the thi- Which clinical features accurately identify WE?
amine status for at least 6 months (Recommendation
Table 4 lists the studies comparing autopsy series
Level B).
(including ‡3 cases) with clinical features of patients
Table 3 List of cases of Wernicke encephalopathy reported in non with acute WE. Most patients were alcoholics. Con-
alcoholic subjectsa secutive autopsies were collected without knowledge of
Clinical condition No. % clinical data. However, it is unknown whether the
clinical data evaluation was blinded to autopsy results;
Cancer 113 18.1 thus all these studies are considered Class IV. The
Gastrointestinal surgery 105 16.8
Hyperemesis gravidarum 76 12.2
classical diagnostic triad (eye signs, cerebellar signs
Starvation/Fasting 64 10.2 and confusion) was reported only in 8% of patients
Gastrointestinal tract diseases 48 7.7 with clinical details. Although it should be considered
AIDS 31 5.0 as a minimum estimate due to a possible reporting
Malnutrition 26 4.2 bias, this figure prompts the need to reconsider
Dialysis and renal diseases 24 3.8
Parenteral nutrition 24 3.8
diagnostic criteria for in-life diagnosis of WE. Caine
Vomiting 15 2.4 et al. [9] (Class II) studied clinical features of 28
Psychiatric diseases 15 2.4 autopsy-proven alcoholic patients with WE that were
Stem cell/marrow transplantation 14 2.2 well-evaluated during life. They divided signs and
Infections 9 1.4 symptoms into eight clinical domains (see Table 4 for
Intoxication 9 1.4
Thyroid diseases 8 1.3
definitions): dietary deficiencies, eye signs, cerebellar
Unbalanced diet 6 1.0 signs, seizures, frontal lobe dysfunction, amnesia, mild
Iatrogenic 5 0.8 memory impairment, and altered mental state.
Hypoxic encephalopathy 2 0.3 Reproducibility and validity of the criteria were then
Others 12 1.9 tested on 106 autopsied alcoholic patients. Clinical
Unknown etiology 19 3.0
Total 625 100.0
records of the patients were blindly reviewed by three
researchers: sensitivity of each domain (recalculated
a
Search performed in Medline, Embase, LILACS from data-base from the paper) ranged from 20% (seizures) to 75%
inception through May 31, 2009.
Table 4 Clinical features of patients with an autopsy proved diagnosis of Wernicke encephalopathy
Cravioto [38] IV 28 14 9 5 26 4
Grunnet [61] IV 24 1 9 3 4 4 17 0
Torvik [41] IV 19 4 0 18 0
Harper [62] IV 97 28 36 29 41 16
Lindboe [46] IV 18 3 0 11 0
Naidoo [49] IV 17 1 8 0 2 9 0
Vege [51] IV 4 2 1 0 0 1 2 3 0
Ogershok [59] IV 4 3 4 1 4 1
Bleggi-Torres [63] IV 8 3 0 6 0
Harper [56] IV 18 0 3 3 6 0
Bertrand [58] IV 19 2 15 19 1 0
Total N (%) 256 21 (8.2) 9 (3.5) 62 (24.2) 65 (25.4) 8 (3.1) 60 (23.4) 136 (53.1) 21 (8.2)
Table 5 Clinical features of alcoholic and non alcoholic patients with Wernicke encephalopathy
Alcoholics
Gallucci [64] IV 5 5 5 4 3 3
Antunez [19] II 15 14 12 10 9
Park [65] III 12 11 10 1 5 4
Varnet [66] IV 25 20 22 19 11
Ogershok [59] IV 6 1 6 3 6 3
Weidauer [67] IV 11 11 10 5 10 9
Chung [68] IV 1 1 0 1 1 0
Halavaara [69] IV 2 1 1 2 2 2 2 2
White [70] IV 1 1 1 1 1 1 1 1
Zuccoli [71] IV 24 22 17 20 13
Total N (%) 102 4 (3.9) 7 (6.9) 92 (90.2) 82 (80.4) 0 (–) 9 (8.8) 77 (75.5) 55 (53.9)
Non alcoholics
Shikata [72] IV 3 3 3 1 3 1
Merkin-Zaborsky [73] IV 3 1 2 3 3 0
Park [65] III 3 2 2 2 2 1 3 2
Ogershok [59] IV 6 6 3 5 2 6 2
Weidauer [67] IV 1 1 1 1 1 1 1
Chung [68] IV 3 1 0 1 3 3 1
Halavaara [69] IV 3 3 2 3 3 1 2 2
Zhong [74] IV 6 6 2 2 2 6
White [70] IV 2 2 2 2 2 1 1 1
Sun [75] IV 4 1 3 3 0 1 4 0
Unlu [76] IV 6 6 6 6 6 6
Fei [77] IV 12 12 9 3 3 2
Kirbas [78] IV 25 25 7 14 10 9 4
Francini-Pesenti [80] IV 7 7 3 6 7 7 6
Zuccoli [71] IV 32 21 11 22 13 30 11
Total 116 96 (82.8) 36 (31.0) 82 (70.7) 58 (50.0) 0 (–) 13 (11.2) 78 (67.2) 39 (33.6)
Empty cell = not mentioned; 0 = specified as absent. See Table 4 for the definition of domains.
frequently present as a subclinical syndrome. Fur- additional paper alcoholics with acute WE to controls
thermore, alcoholics may develop thiamine deficiency and asymptomatic alcoholics without WE. In this Class
several times during their life span, whereas non II retrospective study alcoholics with and without WE
alcoholics are not likely to do so. Magnesium defi- were compared and MRIs were randomly and blindly
ciency could also contribute to the poor recovery assessed by two neuroradiologists [19]. The sensitivity
from WE in alcoholics [14]. and specificity of MRI were 53% and 93%. Positive
predictive value was 89%.
Recommendation Pooled data in Table 6 showed that among alcoholics
The clinical diagnosis of WE should take into account with a clinically verified acute WE, conventional MRI
the different presentations of clinical signs between revealed lesions in nearly two-thirds of the subjects.
alcoholics and non alcoholics and the higher prevalence Little additional information was obtained by using
of the disease in alcoholics (Level C). fluid-attenuated inversion recovery (FLAIR) images
and diffusion-weighted imaging (DWI). In non alco-
holics, the available data showed a higher yield of
Is there any laboratory test that accurately identifies
lesions varying from 97% (DWI), 99% (conventional)
patients with thiamine deficiency?
and 100% (FLAIR). Location of lesions was more
The erythrocyte transketolase activity assay including frequently atypical among non alcoholic than alcoholic
thiamine pyrophosphate effect has been replaced by patients whereas contrast enhancement of the thalamus
direct measurement of thiamine and its phosphate and mamillary bodies was observed to associate more
esters in human blood by high-performance liquid frequently with alcohol abuse [20]. Typically, the lesions
chromatography (HPLC) [15,16]. This thiamine assay is were symmetrical and seen in the thalami, mamillary
now commercially available in many countries. Adult bodies, tectal plate and periaqueductal area. Atypical
normal range (60–220 nM) and the lowest detectable lesions were located in the cerebellum, vermis, cranial
level (3–35 nM) are given. The sample (2 ml EDTA nerve nuclei, red nuclei, dentate nuclei, caudate nuclei,
blood) should be taken before administration of thia- splenium and cerebral cortex. Reversible cytotoxic
mine and should be protected from light. However, edema was considered the most distinctive lesion of WE
normal thiamine levels do not necessarily exclude WE [20]. The heterogeneity of MRI lesions may result from
in exceptional cases, i.e. in the presence of thia- disease severity, acuteness of the disease and timing of
mine transporter gene mutations [17]. imaging. We cannot say which of the MRI techniques
The concentration of thiamine and thiamine mono- used is most useful.
phosphate and diphosphate in plasma and whole blood
samples were assessed in six healthy subjects for 12 h Recommendation
and in urine for 24 h following either intravenous or MRI is a powerful tool which should be used to support
oral bolus dose of 50 mg thiamine HCl. Unphosphor- the diagnosis of acute WE both in alcoholics and non
ylated thiamine increased rapidly in plasma after alcoholics (level B). It could also be used to follow the
intravenous administration and then decreased to its recovery of patients.
initial value within 12 h. The half-life was 96 min.
Thiamine mono and diphosphate increased moderately
What is the efficacy of thiamine treatment in WE?
(56%), and decreased slowly; the half-life of diphos-
phate was 664 min. Within 24 h, 53% of the adminis- The efficacy of thiamine for WE has been assessed in
tered dose was recovered in the urine, indicating a only one double-blind randomized clinical trial [21].
restricted distribution [18]. Due to several methodological shortcomings it is in our
opinion a class III study. Thiamine hydrochloride was
Recommendation given to 107 patients in doses of 5, 20, 50, 100 and
Whenever WE is suspected a blood sample for mea- 200 mg im daily for 2 days, with assessment of effect on
surement of total thiamine should be drawn immedi- the third day by a single neuropsychological test, sug-
ately before administration of thiamine and sent for gested to be sensitive to cognitive impairment. The
HPLC analysis (GPP). authors concluded that the 200 mg dose was superior to
the mean result of all the other dosages. This study was
evaluated in a Cochrane review concluding that in
Does radiology accurately identify patients with WE?
comparison to the 5 mg dose 200 mg was significantly
CT scanning is not a reliable test for WE [19] (Class II). more effective [22]. In another randomized double-blind
Table 6 lists MRI series including ‡3 cases of WE. study 10 mg thiamine or placebo were given to elderly
Seven compare alcoholics to non alcoholics and one people with subclinical thiamine deficiency [23]. These
people did not have WE. Quality of life was enhanced drome may have resulted in permanent damage of the
by providing thiamine supplements. brain tissue due to excess glutamate liberated in the
There is no consensus on the optimal dose of thi- brain [27].
amine, its preparation form, duration of treatment, or Experimental [18] and clinical data [28–30] indicate
the number of daily doses. Pharmacokinetic studies that orally administered thiamine hydrochloride is inef-
show a blood half-life of free thiamine of only 96 min fective in increasing blood thiamine or curing WE. The
[18] so it can be speculated that giving thiamine in critical blood concentrations of thiamine for treating WE
two or three daily doses might achieve better pene- have not been determined. It could be speculated that
trance to the brain and other tissues than a single patients in a catabolic state and alcoholics have reduced
daily dose [24]. ability to store thiamine because the enzymes depending
According to many case reports, treatment with on thiamine are down regulated or protein binding is
either 100 or 200 mg thiamine given intravenously has altered by the influence of alcohol. In such patients
cured the disease in non alcoholics. On the other even high doses of thiamine might not cause a sufficient
hand, this has not always been the case in alcoholics. increase of thiamine stores unless a balanced diet has
Alcoholic patients with WE may need higher daily been instituted at the same time. Thus, normalization of
doses and 500 mg three times daily has been recom- diet might be an important factor in the acute treatment
mended [25,26]. The reason for the discrepancy is of suspected or manifest WE.
unclear. Alcoholics may have had previous subclinical As the unwanted side-effects to B vitamins are
episodes of the disease leading to permanent damage most commonly seen after multiple administrations,
in the brain before admission to hospital with WE or and the necessary dose of thiamine amounts to a
the often coexistent severe alcohol withdrawal syn- rather painful volume when given intramuscularly, we
Table 6 MRI features of alcoholic and non alcoholic patients with Wernicke encephalopathy
Conventional MRI-Gadolinium
MRI enhancement FLAIR MRI DWR MRI
Evidence Type of Total Positive Total Positive Total Positive Total Positive
class MRI no. no. (%) no. no. (%) no. no. (%) no. no. (%)
Alcoholics
Gallucci [64] IV 0.5 T 5 5
Antunez [19] II 1.5 T 15 8 2 0
Park [65] III 2.0 T 8 8
Varnet [66] III 1.0/1.5 T 25 16 25 3
Ogershok [59] IV ? 2 0
Chung [68] IV 1.5 T 1 1
Weidauer [67] IV 1.5 T 11 2 11 4 11 3
Halavaara [69] IV 1.5 T 2 2 2 0 2 2 2 2
White [70] IV ? 1 1 1 1 1 1
Zuccoli [71] IV 1.0/1.5 T 24 17 18 17 24 17
Total 93 59 (63.4) 58 24 (41.4) 38 23 (60.5) 4 4 (100)
Non alcoholics
Mascalchi [79] IV ? 3 3 2 1
Park [65] III 2.0 T 3 3
Ogershok [59] IV ? 1 1
Chung [68] IV 1.5T 1 1 1 1 1 1 1 1
Weidauer [67] IV 1.5 T 1 0 1 1 1 1
Halavaara [69] IV 1.5 T 3 3 3 0 3 3 3 3
White [70] IV ? 2 2 2 2 2 2
Zhong [74] IV 1.5 T 6 6 6 6
Unlu [76] IV 1.0 T 6 6 6 5 6 6 6 6
Fei [77] IV 1.5 T 12 12 3 3 10 10 4 3
Francini-Pesenti [80] IV ? 7 7 7 7 7 7
Zuccoli [71] IV 1.0/1.5 T 32 32 23 9 32 32
Total 77 76 (98.7) 43 22 (51.0) 72 72 (100) 29 28 (97.0)
suggest an intravenous infusion of thiamine diluted tional studies from Australia [33,34] suggest that this
with 100 ml of normal saline or 5% glucose, given preventive effort has resulted in a decrease of the
over 30 min. occurrence of the disease, although no controlled
It is also important to give thiamine before any car- studies have been performed on this matter and are
bohydrate, because it is well known that glucose infu- unlikely to be done in the future. Supplementation of
sion precipitates WE in thiamine deficiency [26]. thiamine to alcoholic beverages has been suggested too
[32]. However, the mechanisms via which alcohol
Recommendation ingestion predisposes to thiamine deficiency suggest
There is sufficient evidence that thiamine is indicated that adding thiamine into alcoholic beverages is a use-
for the treatment of suspected or manifest WE (level C). less strategy. First, alcohol inhibits the absorption of
Since studies of sufficient quality to warrant a formal thiamine from the intestine; second, during alcohol
recommendation are lacking, there is no evidence to metabolism thiamine will neither be phosphorylated
support conclusions as to dosage, route of administra- nor incorporated to enzymes in body tissues [35]. Thi-
tion, and treatment time. However, we recommend that amine ingested together with alcohol will be excreted in
thiamine should be given 200 mg three times daily and urine as free thiamine.
preferably via intravenous instead of intramuscular Thiamine deficiency is frequently not clinically
route (level C). Thiamine should be given before any apparent and WE can easily be worsened or precipi-
carbohydrate, and a normal diet should be instituted tated if the treating physician gives glucose to a patient
immediately after thiamine (GPP). Treatment should be unaware that there is thiamine deficiency. In many
continued until there is no further improvement in signs countries emergency ward guidelines include recom-
and symptoms (GPP). mendations to administer parenteral thiamine, e.g., to
patients who are in status epilepticus [36] before any
infusion of carbohydrates is started.
Is thiamine therapy safe?
There are also other conditions (Table 3) in which
The overall safety of intravenous thiamine is very good. administration of thiamine in food or oral preparation
In a prospective study of 989 patients receiving 100 mg is inefficient (e.g. vomiting). Such conditions require
thiamine hydrochloride as a single intravenous injection parenteral administration of thiamine. In hunger
over 10 s or less, one patient reacted with generalized strikers there is evidence from one cohort study (Class
pruritus and 11 had transient local irritation [31] (Class IV) [37] that up to 600 mg. thiamine orally together
II). In a retrospective survey Wrenn and Slovis [31] with one tablespoon of sugar daily did not prevent the
identified no cases of significant adverse reactions to development of WE. We did not find any other studies
thiamine in more than 300.000 treatments. Sporadic evaluating the prophylactic administration of thiamine
anaphylactic reactions have been reported, but it is not in other risk conditions in alcoholics or in non alco-
documented that thiamine was the cause in all cases. holics. Administration of multivitamin pills has been
However, it has been suggested that thiamine should be recommended following bariatric surgery. However,
given in circumstances where facilities for resuscitation parenteral administration of vitamins may be a better
are available [25]. This is preferable, but because a delay strategy to prevent vitamin deficiency, because these
in treatment may cause irreversible brain damage and is patients frequently vomit [7].
life-threatening we recommend to start treatment
immediately, even in the absence of facilities for resus- Recommendation
citation. Supplementation of thiamine to food may prevent the
development of WE (GPP). There is no evidence that
Recommendation supplementation to beverages may be useful. We
The overall safety of thiamine is very good, regardless recommend prophylactic parenteral administration of
of route of administration (level B). Thiamine should be 200 mg thiamine before carbohydrates are started in
given without delay in all circumstances irrespective of all subjects with a risk condition managed at the
whether facilities for resuscitation are immediately Emergency Room (GPP). After bariatric surgery we
available or not (GPP). recommend parenteral thiamine supplementation
(GPP). We think that hunger strikers should be
carefully informed of the risk of WE and persuaded
Is there a place for prophylactic thiamine therapy?
to accept a parenteral administration of thiamine
Studies from several countries show a thiamine defi- followed by glucose (GPP). However, in both these
ciency in the elderly population [32]. Thiamine has been situations we do not have any evidence of an effective
added to foods in many countries [33]. Some observa- dosage.
35. Hoyumpa AM Jr. Mechanisms of thiamin deficiency in 55. Sheedy D, Lara A, Garrick T, Harper C. Size of mamil-
chronic alcoholism. Am J Clin Nutr 1980; 33: 2750– lary bodies in health and disease: useful measurements in
2761. neuroradiological diagnosis of WernickeÕs encephalopa-
36. Meierkord H, Boon P, Engelsen B, et al. EFNS guideline thy. Alcohol Clin Exp Res 1999; 23: 1624–1628.
on the management of status epilepticus in adults. Eur J 56. Harper CG, Sheedy DL, Lara AI, Garrick TM, Hilton
Neurol 2010; 17: 348–355. JM, Raisanen J. Prevalence of Wernicke-Korsakoff syn-
37. Basoglu M, Yetimalar Y, Gurgor N, et al. Neurological drome in Australia: has thiamine fortification made a
complications of prolonged hunger strike. Eur J Neurol difference? Med J Aust 1998; 168: 542–545.
2006; 13: 1089–1097. 57. Bleggi-Torres LF, de Medeiros BC, Werner B, et al.
38. Cravioto H, Korein J, Silberman J. WernickeÕs encepha- Neuropathological findings after bone marrow trans-
lopathy. A clinical and pathological study of 28 autopsied plantation: an autopsy study of 180 cases. Bone Marrow
cases. Arch Neurol 1961; 4: 510–519. Transplant 2000; 25: 301–307.
39. Jellinger K. Neuropathological aspects of dementias 58. Bertrand A, Brandel JP, Grignon Y, et al. Wernicke
resulting from abnormal blood and cerebrospinal fluid encephalopathy and Creutzfeldt-Jakob disease. J Neurol
dynamics. Acta Neurol Belg 1976; 76: 83–102. 2009; 256: 904–909.
40. Victor M, Adams RD, Collins GH. The Wernicke-Kor- 59. Ogershok PR, Rahman A, Nestor S, Brick J. Wernicke
sakoff syndrome. A clinical and pathological study of 245 encephalopathy in nonalcoholic patients. Am J Med Sci
patients, 82 with post-mortem examinations. Contemp 2002; 323: 107–111.
Neurol Ser 1971; 7: 1–206. 60. Kuo SH, Debnam JM, Fuller GN, de Groot J. WernickeÕs
41. Torvik A, Lindboe CF, Rogde S. Brain lesions in alco- encephalopathy: an underrecognized and reversible cause
holics. A neuropathological study with clinical correla- of confusional state in cancer patients. Oncology 2009; 76:
tions. J Neurol Sci 1982; 56: 233–248. 10–18.
42. Harper C. WernickeÕs encephalopathy: a more common 61. Grunnet ML. Changing incidence, distribution and his-
disease than realised. A neuropathological study of 51 topathology of WernickeÕs polioencephalopathy. Neurol-
cases. J Neurol Neurosurg Psychiatry 1979; 42: 226–231. ogy 1969; 19: 1135–1139.
43. Harper C. The incidence of WernickeÕs encephalopathy 62. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the
in Australia – a neuropathological study of 131 cases. Wernicke-Korsakoff complex: a retrospective analysis of
J Neurol Neurosurg Psychiatry 1983; 46: 593–598. 131 cases diagnosed at necropsy. J Neurol Neurosurg
44. Hauw JJ, De Baecque C, Hausser-Hauw C, Serdaru M. Psychiatry 1986; 49: 341–345.
Chromatolysis in alcoholic encephalopathies. Pellagra- 63. Bleggi-Torres LF, de Medeiros BC, Ogasawara VS, et al.
like changes in 22 cases. Brain 1988; 111: 843–857. Iatrogenic WernickeÕs encephalopathy in allogeneic bone
45. Harper C, Gold J, Rodriguez M, Perdices M. The prev- marrow transplantation: a study of eight cases. Bone
alence of the Wernicke-Korsakoff syndrome in Sydney, Marrow Transplant 1997; 20: 391–395.
Australia: a prospective necropsy study. J Neurol Neuro- 64. Gallucci M, Bozzao A, Splendiani A, Masciocchi C,
surg Psychiatry 1989; 52: 282–285. Passariello R. Wernicke encephalopathy: MR findings in
46. Lindboe CF, Loberg EM. WernickeÕs encephalopathy in five patients. AJR Am J Roentgenol 1990; 155: 1309–1314.
non-alcoholics. An autopsy study. J Neurol Sci 1989; 90: 65. Park SH, Kim M, Na DL, Jeon BS. Magnetic resonance
125–129. reflects the pathological evolution of Wernicke encepha-
47. Pollak KH. Alcoholism and morphologic findings of the lopathy. J Neuroimaging 2001; 11: 406–411.
nervous system in autopsy cases. Psychiatr Neurol Med 66. Varnet O, de Seze J, Soto-Ares G, et al. Wernicke-Kor-
Psychol (Leipz) 1989; 41: 664–679. sakoff syndrome: diagnostic contribution of magnetic
48. Skullerud K, Andersen SN, Lundevall J. Cerebral lesions resonance imaging. Rev Neurol (Paris) 2002; 158: 1181–
and causes of death in male alcoholics. A forensic autopsy 1185.
study. Int J Legal Med 1991; 104: 209–213. 67. Weidauer S, Nichtweiss M, Lanfermann H, Zanella FE.
49. Naidoo DP, Bramdev A, Cooper K. WernickeÕs enceph- Wernicke encephalopathy: MR findings and clinical pre-
alopathy and alcohol-related disease. Postgrad Med J sentation. Eur Radiol 2003; 13: 1001–1009.
1991; 67: 978–981. 68. Chung SP, Kim SW, Yoo IS, Lim YS, Lee G. Magnetic
50. Riethdorf L, Warzok R, Schwesinger G. Die Alkoholen- resonance imaging as a diagnostic adjunct to Wernicke
zephalopathien im Obduktionsgut. Zentralbl Pathol 1991; encephalopathy in the ED. Am J Emerg Med 2003; 21:
137: 48–56. 497–502.
51. Vege A, Sund S, Lindboe CF. WernickeÕs encephalopathy 69. Halavaara J, Brander A, Lyytinen J, Setala K, Kallela M.
in an autopsy material obtained over a one-year period. WernickeÕs encephalopathy: is diffusion-weighted MRI
APMIS 1991; 99: 755–758. useful? Neuroradiology 2003; 45: 519–523.
52. Lana-Peixoto MA, Dos Santos EC, Pittella JE. Coma and 70. White ML, Zhang Y, Andrew LG, Hadley WL. MR
death in unrecognized WernickeÕs encephalopathy. An imaging with diffusion-weighted imaging in acute and
autopsy study. Arq Neuropsiquiatr 1992; 50: 329–333. chronic Wernicke encephalopathy. AJNR Am J Neuro-
53. Boldorini R, Vago L, Lechi A, Tedeschi F, Trabattoni radiol 2005; 26: 2306–2310.
GR. WernickeÕs encephalopathy: occurrence and patho- 71. Zuccoli G, Santa Cruz D, Bertolini M, et al. MR imaging
logical aspects in a series of 400 AIDS patients. Acta findings in 56 patients with Wernicke encephalopathy:
Biomed Ateneo Parmense 1992; 63: 43–49. nonalcoholics may differ from alcoholics. AJNR Am J
54. Harper C, Fornes P, Duyckaerts C, Lecomte D, Hauw JJ. Neuroradiol 2009; 30: 171–176.
An international perspective on the prevalence of the 72. Shikata E, Mizutani T, Kokubun Y, Takasu T. ÔIatro-
Wernicke-Korsakoff syndrome. Metab Brain Dis 1995; 10: genicÕ WernickeÕs encephalopathy in Japan. Eur Neurol
17–24. 2000; 44: 156–161.
73. Merkin-Zaborsky H, Ifergane G, Frisher S, Valdman S, encephalopathy. AJNR Am J Neuroradiol 2008; 29: 164–
Herishanu Y, Wirguin I. Thiamine-responsive acute neu- 169.
rological disorders in nonalcoholic patients. Eur Neurol 78. Kirbas D, Sutlas N, Kuscu DY, Karagoz N, Tecer O,
2001; 45: 34–37. Altun U. The impact of prolonged hunger strike: clinical
74. Zhong C, Jin L, Fei G. MR Imaging of nonalcoholic and laboratory aspects of twenty-five hunger strikers.
Wernicke encephalopathy: a follow-up study. AJNR Am J Ideggyogy Sz 2008; 61: 317–324.
Neuroradiol 2005; 26: 2301–2305. 79. Mascalchi M, Simonelli P, Tessa C, et al. Do acute lesions
75. Sun GH, Yang YS, Liu QS, Cheng LF, Huang XS. of WernickeÕs encephalopathy show contrast enhance-
Pancreatic encephalopathy and Wernicke encephalopathy ment? Report of three cases and review of the literature
in association with acute pancreatitis: a clinical study. Neuroradiology 1999; 41: 249–254.
World J Gastroenterol 2006; 12: 4224–4227. 80. Francini-Pesenti F, Brocadello F, Manara R, Santelli L,
76. Unlu E, Cakir B, Asil T. MRI findings of Wernicke Laroni A, Caregaro L. WernickeÕs syndrome during par-
encephalopathy revisited due to hunger strike. Eur J enteral feeding: not an unusual complication. Nutrition
Radiol 2006; 57: 43–53. 2009; 25: 142–146.
77. Fei GQ, Zhong C, Jin L, et al. Clinical characteristics
and MR imaging features of nonalcoholic Wernicke