Scientific Letter
Progressive encephalopathy associated with nutritional deficiencies: Identifying patients at high risk for developing thiamine deficiency
Encefalopatía progresiva de origen carencial: identificar a los pacientes en riesgo de déficit de tiamina
M.D. Freire-Aragón, E. Fernández Delgado
, J. Carbajal-Guerrero, G. Ribera-Rubiales
Corresponding author
Unidad de Neurocríticos, Unidad de Cuidados Intensivos, Hospital Universitario Virgen del Rocío, Sevilla, Spain
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Fernández Delgado, J. Carbajal-Guerrero, G. Ribera-Rubiales" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.D." "apellidos" => "Freire-Aragón" ] 1 => array:4 [ "nombre" => "E." "apellidos" => "Fernández Delgado" "email" => array:2 [ 0 => "esperanzafernandezdelgado@gmail.com" 1 => "complejodewendy@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Carbajal-Guerrero" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Ribera-Rubiales" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Neurocríticos, Unidad de Cuidados Intensivos, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Encefalopatía progresiva de origen carencial: identificar a los pacientes en riesgo de déficit de tiamina" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 946 "Ancho" => 1600 "Tamanyo" => 114912 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Axial FLAIR MRI sequence: hyperintense lesions at periaqueductal level and around the third ventricle confirmed–all of them typical of Wernicke's encephalopathy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Wernicke's encephalopathy (WE) is a neurological entity due to thiamine deficiency that is classically associated with alcoholism although it may be present in non-alcoholics too.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> Its estimated prevalence is 0.4–2.8 per cent, but the coexistence of conditions of the same profile and the inaccessibility to diagnostic tests make the real incidence of this condition unknown.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Due to the severity and innocuousness of the treatment, the immediate administration of thiamine is recommended and it stops the progression of the disease and favours recovery.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3</span></a> In order to prevent the occurrence of WE, we should know all those therapeutic situations and interventions where there is an increased metabolic demand that may lead to its deficiency.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> In view of this situation, we hereby present the case of one female patient with thiamine deficient-encephalopathy of rapid progression.</p><p id="par0010" class="elsevierStylePara elsevierViewall">It is the case of a fifty-seven year old female with a history of duodenal bulbitis only. She had been experiencing compartmental alterations, vertigo, vomit, abdominal pain, and food intolerance for two (2) months that finally lead to acute renal failure, and severe metabolic acidosis that ended up with the patient being admitted to her reference hospital. At admission, symptomatic treatment and fluid therapy was initiated and renal function was recovered, but the persistence of the patient's digestive clinical manifestations recommended the initiation of parenteral nutrition (PN). One abdominal computed tomography (CT) scan was performed together with one digestive endoscopy, and several other serological and microbiological tests–all of them with anodyne results. In a progressive way, the behavioural changes became more and more significant and deteriorated the patient's level of consciousness until she scored 9–10 points in the Glasgow Coma Scale (GCS). One cranial CT scan and one lumbar puncture were performed and both were not pathological. Given the diagnostic uncertainty, the patient was transferred to our unit specialised in the management of neurocritical conditions.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Upon arrival the patient scored 8–12 points in the GCS. Her only physical focality was the inexistence of oculocephalic reflexes. Given the patient's clinical manifestations, chronopathology, and negative tests, the initial suspicion included the possibility of WE and the patient was administered IV thiamine; 24–48<span class="elsevierStyleHsp" style=""></span>h later the patient improved significantly and was bradypsychic, yet aware and collaborative. One cranial MRI was performed that confirmed the presence of thalamic, periaqueductal hyperintense, symmetrical lesions, mammillary bodies and quadrigeminal tubercles–all typical findings of WE and the patient was discharged early. Yet despite the patient's initial recovery, in the posterior follow-ups she showed sequelae noticeable in her gait and memory.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There are multiple publications on WE. The classical clinical triad includes the alteration of the mental state, oculomotor signs and cerebellous alterations.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> The coexistence of these symptoms is variable, but the series coincide in that this entity is more common in alcoholic patients than in non-alcoholic patients, in whom the course of the disease is faster and more fatal, making it detection harder.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3</span></a> The diagnostic sensitivity of the triad is limited (20 per cent), but it improves when nutritional deficit is included: if 2 out of these 4 symptoms are present, we may detect up to 85 per cent,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> coexisting all in our case. However, occasionally it is done by exclusion.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The thiamine reserves are limited and we need a regular supply in our food.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> It is hydrolysed in the stomach and its local absorption is saturable, which is why its oral administration is not effective if we want to increase its levels rapidly,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> being the parenteral administration essential.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3,5</span></a> Its function is being the cofactor of enzymes of the metabolism of carbohydrates that are essential in the production of cerebral energy, and its deficit<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a> causes neurotoxicity, and neuronal death.</p><p id="par0030" class="elsevierStylePara elsevierViewall">If there is insufficient intake or incremental losses, its deposits are depleted in 3–4 weeks.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Intake after prolonged fasting and/or the administration of glucose solutions increases the needs, which is why it is recommended to administer it before or together with glucose solutions.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Its leading cause is alcoholism although it may be due to malnutrition, losses (vomits, dialysis), increased requirements (severe sepsis, burned) and genetic metabolic disorders,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> being the coexistence of various of these factors the ideal scenario for its rapid progression. In our case, prolonged hyperemesis was initially responsible, although the introduction of PN increased the metabolic demand in one patient in whom the deficit was unnoticed, which worsened the progression. Multivitamin supplements usually include between 3 and 3.5<span class="elsevierStyleHsp" style=""></span>mg of thiamine. Based on the actual guidelines, patients at risk who initiate PN should receive between 100 and 300<span class="elsevierStyleHsp" style=""></span>mg/day during the first three (3) days,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3,6</span></a> especially patients with malnutrition.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> However, compliance is poor. There is no general consensus on dose in WE.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Diagnosis is clinical even though there are tests for assessment and support. The cerebral nuclear magnetic resonance is the modality of choice<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3</span></a> thanks to its specificity (93 per cent) and positive predictive value (89 per cent) being the CT scan discarded due to its low sensitivity. The typical lesions are symmetrical and they affect the medial thalamus, the mammillary bodies, the tectal plate, and the periaqueductal region<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The thiamine deficiency may be analysed using high resolution liquid chromatography or from the activity displayed by erythrocyte transketolase<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3,7</span></a> where it acts as a cofactor. In our patient we were unable to obtain any levels due to an extraction mistake that made our sample useless. The fast recovery after the administration is the best diagnosis as it occurred with our patient.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Vitamins and other coexisting deficits should be supplemented. Magnesium is an important cofactor of the thiamine pathways. One recent study confirmed a significant increase of the activity of erythrocyte transketolase in the group treated with magnesium and thiamine compared to the group that received thiamine only, which means that the administration of magnesium plus thiamine may speed up the recovery of metabolic pathways.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The prognosis of WE is closely associated with the precocity of diagnosis and treatment.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3,5</span></a> Its low cost and innocuousness support its early administration. The residual deficits are common as it occurred with the case presented here.</p><p id="par0055" class="elsevierStylePara elsevierViewall">We would like to finish with a thought. The diagnosis of WE is clinical and the response to treatment with thiamine is the best test there is. We should always take it into consideration with non-related neurological manifestations in patients with risk factors (increased metabolic demand, or deficits). When in clinical suspicion, we should supplement with IV thiamine, since it has a good profile of safety and innocuousness that may prevent and even stop the devastating effects of WE.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have received no funding while conducting this study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Freire-Aragón MD, Fernández Delgado E, Carbajal-Guerrero J, Ribera-Rubiales G. Encefalopatía progresiva de origen carencial: identificar a los pacientes en riesgo de déficit de tiamina. Med Intensiva. 2017;41:439–441.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 946 "Ancho" => 1600 "Tamanyo" => 114912 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Axial FLAIR MRI sequence: hyperintense lesions at periaqueductal level and around the third ventricle confirmed–all of them typical of Wernicke's encephalopathy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 82 | 52 | 134 |
| 2024 September | 110 | 47 | 157 |
| 2024 August | 124 | 46 | 170 |
| 2024 July | 127 | 30 | 157 |
| 2024 June | 122 | 64 | 186 |
| 2024 May | 90 | 35 | 125 |
| 2024 April | 99 | 43 | 142 |
| 2024 March | 97 | 34 | 131 |
| 2024 February | 72 | 54 | 126 |
| 2024 January | 93 | 60 | 153 |
| 2023 December | 123 | 50 | 173 |
| 2023 November | 112 | 84 | 196 |
| 2023 October | 104 | 51 | 155 |
| 2023 September | 104 | 52 | 156 |
| 2023 August | 92 | 32 | 124 |
| 2023 July | 87 | 41 | 128 |
| 2023 June | 99 | 26 | 125 |
| 2023 May | 142 | 38 | 180 |
| 2023 April | 98 | 22 | 120 |
| 2023 March | 133 | 28 | 161 |
| 2023 February | 123 | 35 | 158 |
| 2023 January | 119 | 28 | 147 |
| 2022 December | 123 | 39 | 162 |
| 2022 November | 101 | 37 | 138 |
| 2022 October | 131 | 32 | 163 |
| 2022 September | 120 | 37 | 157 |
| 2022 August | 95 | 48 | 143 |
| 2022 July | 62 | 35 | 97 |
| 2022 June | 70 | 23 | 93 |
| 2022 May | 67 | 37 | 104 |
| 2022 April | 94 | 45 | 139 |
| 2022 March | 107 | 52 | 159 |
| 2022 February | 94 | 36 | 130 |
| 2022 January | 75 | 34 | 109 |
| 2021 December | 84 | 47 | 131 |
| 2021 November | 72 | 35 | 107 |
| 2021 October | 286 | 65 | 351 |
| 2021 September | 72 | 23 | 95 |
| 2021 August | 64 | 41 | 105 |
| 2021 July | 46 | 29 | 75 |
| 2021 June | 47 | 34 | 81 |
| 2021 May | 66 | 48 | 114 |
| 2021 April | 138 | 68 | 206 |
| 2021 March | 78 | 33 | 111 |
| 2021 February | 70 | 28 | 98 |
| 2021 January | 68 | 25 | 93 |
| 2020 December | 63 | 28 | 91 |
| 2020 November | 59 | 21 | 80 |
| 2020 October | 64 | 34 | 98 |
| 2020 September | 51 | 15 | 66 |
| 2020 August | 52 | 19 | 71 |
| 2020 July | 112 | 21 | 133 |
| 2020 June | 44 | 13 | 57 |
| 2020 May | 62 | 17 | 79 |
| 2020 April | 46 | 9 | 55 |
| 2020 March | 27 | 5 | 32 |
| 2020 February | 78 | 23 | 101 |
| 2020 January | 46 | 25 | 71 |
| 2019 December | 106 | 21 | 127 |
| 2019 November | 44 | 33 | 77 |
| 2019 October | 37 | 22 | 59 |
| 2019 September | 37 | 22 | 59 |
| 2019 August | 29 | 22 | 51 |
| 2019 July | 37 | 20 | 57 |
| 2019 June | 28 | 16 | 44 |
| 2019 May | 43 | 24 | 67 |
| 2019 April | 32 | 29 | 61 |
| 2019 March | 29 | 27 | 56 |
| 2019 February | 45 | 39 | 84 |
| 2019 January | 42 | 31 | 73 |
| 2018 December | 69 | 20 | 89 |
| 2018 November | 100 | 41 | 141 |
| 2018 October | 153 | 34 | 187 |
| 2018 September | 58 | 19 | 77 |
| 2018 August | 30 | 8 | 38 |
| 2018 July | 49 | 23 | 72 |
| 2018 June | 53 | 13 | 66 |
| 2018 May | 26 | 10 | 36 |
| 2018 April | 55 | 25 | 80 |
| 2018 March | 154 | 29 | 183 |
| 2018 February | 35 | 15 | 50 |
| 2017 August | 0 | 1 | 1 |
| 2017 July | 0 | 1 | 1 |
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