Wernicke\u2019s encephalopathy (WE) is an acute neurologi- cal disorder, due to a lack of thiamin (vitamin B1) which is observed mainly in alcoholic patients. Unfortunately, the syn- drome is underestimated in clinical practice and most often recognized only on autopsy, especially among non-alcoholics. The common clinical picture include mental status changes, ocular dysfunction, and gait ataxia. Treatment consists of timely thiamine replacement through intravenous infusion.
We describe the case of two patients who developed a non-alcoholic WE post-surgical, regressed completely after intravenous infusion of thiamine. These cases suggest intere- sting diagnostic and therapeutic implications

Brighina, F.

Cosentino, G.

Giglia, F.

Giglia, G.

Panetta, M.

Puma, A.

Talamanca, S.

Vigneri, S.

Wernicke’s encephalopathy (WE) is an acute neurologi- cal disorder, due to a lack of thiamin (vitamin B1) which is observed mainly in alcoholic patients. Unfortunately, the syn- drome is underestimated in clinical practice and most often recognized only on autopsy, especially among non-alcoholics. The common clinical picture include mental status changes, ocular dysfunction, and gait ataxia. Treatment consists of timely thiamine replacement through intravenous infusion.
We describe the case of two patients who developed a non-alcoholic WE post-surgical, regressed completely after intravenous infusion of thiamine. These cases suggest intere- sting diagnostic and therapeutic implications

TALAMANCA, Simona

PUMA, Angela Rita

COSENTINO, Giuseppe

GIGLIA, Giuseppe

PANETTA, Maristella

Vigneri, Simone

Giglia, Francesca

BRIGHINA, Filippo

Archivio Istituzionale della Ricerca - Università degli Studi di Pavia

TWO CASES OF NON-ALCOHOLIC WERNICKE ENCEPHALOPATHY SUCCESSFULLY TREATED BY THIAMINE REPLACEMENT: DIAGNOSTIC AND THERAPEUTIC CONSIDERATIONS

Wernicke’s encephalopathy (WE) is an acute neurologi- cal disorder, due to a lack of thiamin (vitamin B1) which is observed mainly in alcoholic patients. Unfortunately, the syn- drome is underestimated in clinical practice and most often recognized only on autopsy, especially among non-alcoholics. The common clinical picture include mental status changes, ocular dysfunction, and gait ataxia. Treatment consists of timely thiamine replacement through intravenous infusion.
We describe the case of two patients who developed a non-alcoholic WE post-surgical, regressed completely after intravenous infusion of thiamine. These cases suggest intere- sting diagnostic and therapeutic implications

Archivio istituzionale della ricerca - Università di Palermo

SUMMARYWernicke’s encephalopathy (WE) is an acute neurologi-cal disorder, due to a lack of thiamin (vitamin B1) which isobserved mainly in alcoholic patients. Unfortunately, the syn-drome is underestimated in clinical practice and most oftenrecognized only on autopsy, especially among non-alcoholics.The common clinical picture include mental status changes,ocular dysfunction, and gait ataxia. Treatment consists oftimely thiamine replacement through intravenous infusion.We describe the case of two patients who developed anon-alcoholic WE post-surgical, regressed completely afterintravenous infusion of thiamine. These cases suggest intere-sting diagnostic and therapeutic implications.Key words: Wernicke’s encephalopathy, thiamine, total paren-teral nutritionRIASSUNTOL’encefalopatia di Wernicke (EW) è un disordine neuro-logico acuto dovuto ad un deficit di tiamina (vitamina B1) cheinteressa prevalentemente i soggetti alcolisti. Purtroppo, tutta-via, la sindrome è sottodiagnosticata nella pratica clinica e piùspesso riconosciuta solo dopo autopsia, soprattutto tra i non-alcolisti. Il quadro clinico comune comprende alterazioni dellostato mentale, disfunzioni oculari ed atassia. Il trattamentoconsiste nella tempestiva somministrazione di tiamina tramiteinfusione endovenosa.Noi descrivono il caso di due pazienti che sviluppavano unaEW non-alcolica post-chirurgica, che regrediva completamentedopo infusione endovenosa di tiamina. Tali casi suggerisconointeressanti implicazioni diagnostiche e terapeutiche.Parole chiave: Encefalopatia di Wernicke, tiamina, nutrizioneparenterale totaleActa Medica Mediterranea, 2010, 26: 29TWO CASES OF NON-ALCOHOLIC WERNICKE ENCEPHALOPATHY SUCCESSFULLY TREATEDBY THIAMINE REPLACEMENT: DIAGNOSTIC AND THERAPEUTIC CONSIDERATIONSSIMONA TALAMANCA, ANGELA PUMA, GIUSEPPE COSENTINO, GIUSEPPE GIGLIA, MARISTELLA PANETTA, SIMONE VIGNERI,FRANCESCA GIGLIA, FILIPPO BRIGHINAUnit of Neurology, Department of Biomedicina sperimentale e Neuroscienze Cliniche, University of Palermo, Italy - (Head:Giovanni Savettieri)[Due casi di encefalopatia di Wernicke non-alcolica trattati con successo con somministrazione di tiamina:considerazioni diagnostiche e terapeutiche]Introduction Wernicke’s encephalopathy (WE) is an acuteneurological disorder resulting from thiamin (B1vitamin) deficiency, which is observed mainly inalcoholic patients(1). However, in recent years, seve-ral cases of WE were reported to coincide withother clinical settings such as hyperemesis gravida-rum, prolonged fasting, chemotherapy treatments,gastrectomy surgery, tumors or other chronic syste-mic disease(2). Recently, some cases of WE werereported in patients receiving total parenteral nutri-tion (TPN)(3).The diagnosis of WE is primarily based on cli-nical data and medical history. This disorder shouldbe considered in all subjects that show an acuteonset of disturbance of consciousness, possiblyassociated with ataxia and paralysis of gaze. Thepresumptive diagnosis of WE can be confirmed bythe neuroimaging studies. MRI is currentlyconsidered the most value method to confirm thediagnosis of WE. Characteristic findings includebilateral and symmetrical areas of increased signalintensity on T2-weighted and FLAIR images, in thedorsomedial portion of the thalami, in the periaque-ductal region and in the tectum of the midbrain(7-9).MRI sequences DWI showed symmetrical patholo-gic thalamic and midbrain signal hyperintensitiesmore distinctly than did conventional T2-weightedor FLAIR sequences(5,6).We describe two cases of non-alcoholicWernicke's encephalopathy that developed duringtotal parenteral nutrition, due to lack of vitaminsupplementation. This disorder was treated succes-sfully by thiamine administration.Case reports Case 1: A 76-years-old man, in February 2008,was admitted in a department of emergency surgeryfor a history of 2 weeks of rectal bleeding and colicpain in the lower abdominal quadrants. The patientwas suffering from arterial hypertension treated bypharmacological agents, with good control of bloodpressure. He was suffering also from diabetes melli-tus type II complicated by severe lower limbs ische-mia for which he had undergone surgery for amputa-tion of the right leg. It was no reported history ofalcoholism, substance abuse or poor nutrition forstrict diet.A physical examination, including neurologicalstatus, performed at the admission was normal withthe exception of symptoms that had motivated thehospitalization. Laboratory investigations demonstra-ted only a modest sideropenic anemia. During the hospitalization, a colorectal adeno-carcinoma was diagnosed and, in March 2008, thepatient underwent surgical anterior rectal resectionwith colorectal proctoanastomosi. After the surgery,he began a total parenteral feeding regimen that wasprolonged because of a surgical complication (rectalfistula). About 20 days later, the patient acutely presen-ted the onset of symptoms characterized by drowsi-ness, confusion, spatial-temporal disorientation,diplopia and ataxia. A neurological examinationdemonstrated normal size of pupils that were reactedto the light, bidirectional horizontal nystagmus andataxia. The results of electroencephalography (EEG)showed non-specific slowing of the dominant rhytm.A brain computed tomography (CT) showed nosignificant abnormality, except for the presence of amodest cortical-subcortical atrophy. Six days afteronset of clinical symptoms, also a brain magneticresonance imaging (MRI) was performed. T2-weigh-ted and fluid-attenuated inversion recovery (FLAIR)images revealed bilateral and symmetrical hyperin-tense lesions within the dorsomedial thalami, peria-queductal white matter, and in the tectum of the mid-brain (Fig.1a). In addition to conventional MRIsequences, diffusion-weighted imaging (DWI) wereperformed that confirmed more clearly the symme-trical pahologics thalamic and midbrain signalshyperintensities. Cerebrospinal fluid studies wereunremarkable, and viral and bacterial cultures werenegative. Routine blood investigations were unchan-ged from those reported at the admission.Therefore, Wernicke’s encephalopathy was dia-gnosed and the patient was immediately treated withadditional daily thiamine administration (300 mg perday i.v. for 7 consecutive days). Repeated neurologi-cal evaluations revealed a slight but progressiveimprovement in the clinical picture, with completeresolution of symptoms after two months. Remissionof the clinical picture was supported also by neurora-diologic investigations that showed a completeregression of the changes described above.Case 2: A 47-years-old woman, in November2007, was conducted in the emergency area for theoccurrence of recurrent episodes of biliary colic forwhich the patient underwent surgery to videolaparo-tomy-colecistectomy. The medical history showedthe presence of an anxiety-depression syndrome,treated with antipsychotics and an history of gastriculcer treated with gastrectomy surgery and esopha-gus-digiunostomy. Five days later, the patient washospitalized for sudden onset of epigastric acutepain, associated with marked weakness and profusesweating. During hospitalization, a severe acute peri-tonitis secondary to perforation of the gallbladder,complicated by duodenal micro-perforations wasdiagnosed. Therefore, the patient underwent surgicaltreatment. During the postoperative she began a totalparenteral feeding regimen that was prolongedbecause of the onset of acute pancreatitis. Approximately two months after the surgery,the patient presented an acute onset of symptomsincluding gait instability, double vision and psychoticsymptoms as depression and paranoid delusions. Aneurological examination revealed the presence ofdiplopia, vertical spontaneous nystagmus, tremor andataxia with postural instability. Moreover, psycho-motor agitation, drowsiness, confusion and disorien-tation with confabulation, and impaired verbal andnonverbal memory were also evident. Results ofelectroencephalography (EEG) showed non-specificslowing of the dominant rhytm. Cerebrospinal fluidwas normal and showed only a slight increase of pro-tein, while the culture analysis was negative. A brainMRI studies typically demonstrated, in T2-weightedand FLAIR sequences, increased bilateral and sym-metrical signal localized in the paraventricularregions of the thalamus, mammillary bodies, peria-queductal region (Fig.1b). Therefore, the patient waspromptly treated with daily administration of thiami-ne (300 mg per day i.v. for two months). Subsequentneurological evaluations revealed a slight but pro-gressive improvement in the clinical setting. Onlyfour days after the treatment, she was alert andshowed an improvement of memory and orientation,even if she was not yet able to maintain balance orwalk without assistance. Four months after treat-ment, the patient showed complete resolution of neu-rological symptoms. Consistent with this clinicaldata, also neuroimaging showed complete resolutionof changes.30 S. Talamanca - A. Puma et AlDiscussionWernicke’s encephalopathy (WE) is an acuteneurological disorder, clinically characterized byoculomotor disturbances, ataxia and mental-statuschanges. These symptoms may occur singly, butmore often are present in various combinations(4).The most common onset of symptoms is thealtered state of consciousness that occurs more fre-quently as a global confusional state. The patientappears apathetic, inattentive and indifferent toenvironmental stimuli. Spontaneous verbal com-munication is minimal. The memory and learningabilities are impaired. The oculomotor abnormali-ties are represented by nystagmus, paralysis of theabducens and of the conjugate eye movements.The third symptom of the disease is ataxia, whichmanifests primarily as gait instability; in fact disor-ders of the coordination of limbs are rare.Autonomic dysfunction and peripheral neuropathyare also been observed(1).Although alcoholism is responsible for mostcases of WE, in the past two decades it was morefrequently diagnosed in non-alcoholics patientswith a variety of diseases responsible for a state ofsevere nutritional deficiency(2). In addition, recentevidence shows that many patients undergoing aregime of total parenteral nutrition (NPT), due tothe absence of an adequate supplement of thiami-ne, have developed such syndrome in a fewweeks(3).Thiamine deficiency (TD) is the underlyingcause of WE(10). Although the neurologic dysfunc-tion and brain damage that results from TD hasbeen well-described, the precise mechanisms thatlead to the selective histological lesions characteri-stic of this disorder remain unknow. Over the cour-se of many years, various processes have been pro-posed as responsible of the focal neuronal celldeath in this pathological condition(13). Thiamine is an important co-factor of severalenzymes, including the transketolase, pyruvatedehydrogenase el’!-ketoglutarate dehydrogenase.It is essential in maintaining osmotic gradientsacross cell membranes and plays an important roleas a coenzyme in both the Krebs and the pentose-phosphate cycle(4). In its biologically active form,thiamine pyrophosphate (TPP), is an essentialcoenzyme in several biochemical pathways in thebrain(11,12), such as intermediate carbohydrate meta-bolism (for energy production by ATP synthesis),lipid metabolism (for production and maintenanceof myelin sheath), and production of aminoacidsand glucose-derived neurotransmitters (glutamicacid; GABA)(10-13). Therefore, a deficiency of thia-mine in the brain causes a widespread reduction inthe use of glucose, causing mitochondrial damage.Due to the deficient activity of !-ketoglutaratedehydrogenase, an accumulation of glutamateoccurs that, combined with the energy gap, helps todetermine an excito-toxic cell damage[12].We describe two cases of non-alcoholicWernicke's encephalopathy that developed duringtotal parenteral nutrition, due to lack of vitamin sup-plementation.Diagnosis of WE was initially made clinicallyon the basis of the presence of the classic triad inclu-ding ataxia, ocular motility disorders and confusionand successively confirmed by neuroimaging stu-dies. The brain MRI (T2-weighted, FLAIR, DWI)typically showed the characteristics hyperintensitiesthat were symmetrically distributed and localized inthe dorsomedial thalami, periaqueductal white mat-ter, and in the tectum of the midbrain(5-9). The goodresponse to treatment with thiamine finally confir-med the diagnosis. It is interesting note that the com-plete remission of the clinical picture, obtained in afew months, was also in agreement with the neurora-diological data that revealed the complete regressionof the alterations previously described in the brainMRI.Therefore, these cases suggest the need to con-sider the diagnosis of EW in all subjects in NPT thatTwo cases of non-alcoholic Wernicke encephalopathy successfully treated by thiamine replacement... 31Fig.1a-1b:Brain MRI in FLAIRsequences, in the first (Fig.1a) andsecond patient (Fig.1b), showingthe characteristics hyperintensitiesof the WE that are localized, withsymmetrical distribution, in the tec-tum of the midbrain, periaqueduc-tal region and dorsomedial thalami.show an acute onset of mental-status change possiblyassociated with ataxia and oculomotor abnormalities.Although WE is a potentially reversible disorder, itremains a pathologic condition often ignored anduntreated, especially in non-alcoholic patients, sothat it progress towards a fatal evolution. Indeed WEconstitute a medical emergency that, if early recogni-zed and promptly treated, may regress completely ina relatively short period of time. Therefore, inpatients with suspected WE, intravenously thiamineadministration should be initiated immediately. Theprompt parenteral administration of high-dose ofthiamine can arrest disease progression and determi-ne a rapid and complete remission of the neurologi-cal deficits within some weeks or few months. Theremission of clinical picture can be monitored usingneuroradiologic investigations, that may show theregression of those lesions that have not yet reachedthe level of permanent structural alteration.References1) Sechi GP, Serra A. Wernicke’s encephalopathy: new cli-nical settings and recent advances in diagnosis andmanagement. Lancet Neurol 2007; 6: 442–455.2) Michowitz Y, Copel L, Shiloach E, Litovchik I,Rapoport MJ. Non-alcoholic Wernicke’s encephalopat-hy - unusual clinical findings. European Journal ofInternal Medicine 2005; 16: 443-444.3) Pesenti F, Brocadello F, Manara R, Santelli L, LaroniA, Caregaro L. Wernicke's syndrome during parenteralfeeding: not an unusual complication. Nutrition 2009;25: 142-146.4) Thomson AL, Marshall EJ. The Natural History AndPathophysiology Of Wernicke’s Encephalopathy AndKorsakoff’s Psychosis. Alcohol & Alcoholism2006; 41:151–158.5) Halavaara J, Brander A, Lyytinen J, Seta¨la¨ K, KallelaM. Wernicke’s encephalopathy: is diffusion-weightedMRI useful? Neuroradiology 2003; 45: 519-523.6) White ML, Zhang Y, Andrew LG, Hadley WL. MRImaging with Diffusion-Weighted Imaging in Acute andChronic Wernicke Encephalopathy. AJNR Am JNeuroradiol 2005; 26: 2306–2310.7) Zuccoli G, Santa Cruz D, Bertolini M, Rovira A,Gallucci M, Carollo C, Pipitone N. MR ImagingFindings in 56 Patients with Wernicke Encephalopathy:Nonalcoholics May Differ from Alcoholics. AJNR Am JNeuroradiol. 2009; 30: 171-176.8) Weidauer S, Nichtweiss M, Lanfermann H, Zanella FE.Wernicke encephalopathy: MR findings and clinicalpresentation. Eur Radiol 2003; 13: 1001–1009.9) Sang-Jin Baea, Ho Kyu Leea, Jae-Hong Leea, ChoongGon Choia and Dae Chul Suha. Wernicke’sEncephalopathy: Atypical Manifestation at MRImaging. American Journal of Neuroradiology 2001;22: 1480-1482. 10) Martin PR, Singleton CK, Hiller-Sturmhöfel S. Therole of thiamine deficiency in alcoholic brain disease.Alcohol Res Health. 2003; 27: 134-142.11) Butterworth RF. Effects of thiamine deficiency on brainmetabolism: implications for the pathogenesis of theWernicke-Korsakoff syndrome. Alcohol Alcohol. 1989;24: 271-279. 12) Bâ A. Metabolic and structural role of thiamine in ner-vous tissues. Cell Mol Neurobiol. 2008; 7: 923-931. 13) Hazell AS. Astrocytes are a major target in thiaminedeficiency and Wernicke's encephalopathy. NeurochemInt. 2009; 5: 129-135.__________Request reprints fromDott. 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TWO CASES OF NON-ALCOHOLIC WERNICKE ENCEPHALOPATHY SUCCESSFULLY TREATED BY THIAMINE REPLACEMENT: DIAGNOSTIC AND THERAPEUTIC CONSIDERATIONS

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