Mar 7, 2005 - receiving multivitamin products containing thiamine for other reasons or to eating food even during conditioning. In conclusion, although WE is ...
Bone Marrow Transplantation (2005) 35, 829–830 & 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00
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Correspondence Wernicke’s encephalopathy after allogeneic stem cell transplantation Bone Marrow Transplantation (2005) 35, 829–830. doi:10.1038/sj.bmt.1704893 Published online 7 March 2005 Allogeneic stem cell transplantation (allo-SCT) is the treatment of choice for a variety of hematological, nonhematological, genetic, and immune diseases. However, aside from the prolonged neutropenia and risk of opportunistic infection, the conditioning therapy can cause many side effects including nausea, vomiting, mucositis, and diarrhea,1 leading to a reduced caloric intake and malabsorption, and necessitating total parenteral nutrition (TPN) regimens in recipients. Wernicke’s encephalopathy (WE) is a metabolic disorder caused by a deficiency of thiamine, which plays an important role as a coenzyme in the Krebs and pentosephosphate cycles.2 The disease is most frequently associated with chronic alcoholism, yet can also occur in relation to other forms of malnutrition or malabsorption3 such as prolonged TPN, total gastrectomy, gastrojejunostomy, severe anorexia, or hyperemesis gravidarum. We present a case of acute WE occurring after allogeneic peripheral blood stem cell transplantation (PBSCT) associated with prolonged use of a commercial TPN product. A 42-year-old female with acute myeloid leukemia underwent allogeneic PBSCT from an HLA-matched sister. She received a conditioning regimen consisting of intravenous (i.v.) busulfan and cyclophosphamide. GVHD prophylaxis was with cyclosporin A and a short course of methotrexate. The transplanted cell dose was 3.46 108 MNCs/kg including 7.12 106 CD34 þ /kg. The patient complained of severe anorexia and nausea from day þ 1 and could not eat any food until day þ 37. TPN was administered from day þ 2 and commercial TPN solutions prescribed for nutrition. Neutrophil engraftment (absolute neutrophil count X0.5 109/l) was evident on day þ 14 and platelet engraftment (X20 109/l) was reached on day þ 20. A bone marrow aspirate taken on day þ 22 showed normal cellularity with no evidence of residual disease. On day þ 27, the patient complained of generalized weakness, dizziness, gait disturbance, and restlessness. Neurological examination revealed mild confusion, bilateral horizontal nystagmus with full eyeball movements, mild bilateral lower limb ataxia, and truncal ataxia. Meanwhile, magnetic resonance imaging of the brain showed an increased signal in the mamillary bodies in fluid-attenuated inversion recovery images. The mamillary bodies were enhanced following a contrast injection in T1-weighted images, yet normal in noncontrasted T1-weighted images (Figure 1). With the impression of WE, the patient was immediately given i.v. thiamine 300 mg/day from day þ 35, and 2 days later, her general condition and neurologic signs were much improved. After 1 week of thiamine treatment, the
Figure 1 Magnetic resonance imaging of brain shows increased signal in mamillary bodies in fluid-attenuated inversion recovery images (a) and exhibits enhanced mamillary bodies following contrast injection in T1-weighted images (b).
neurological signs and gastrointestinal symptoms disappeared, although minimal nystagmus persisted with gradual improvement. On day þ 43, the patient was discharged, and at the last follow-up (day þ 133), a stable condition was reported without any sequelae of WE. WE caused by thiamine deficiency is characterized by a triad of altered mentation, ataxia, and ocular abnormalities.4 WE is not usually found in patients undergoing aggressive chemotherapy5 or SCT.6 When present, WE is frequently associated with the long-term use of TPN and protracted vomiting.7 Ocular signs, including ophthalmoplegia, horizontal and vertical nystagmus, and conjugate gaza palsies, are the hallmark of WE. However, it has also been shown that patients with WE can develop a variety of symptoms in addition to or in place of the classical triad. Disease onset can be gradual, evolving over several days. Clinical and pathological studies have indicated that an altered mental status is present in 82–90%, ataxia in 23– 70%, and ocular signs in 29–93%. It has also been found that only 16% of patients show the classical triad and 19% have no clinical signs. Neurological complications are fairly common in patients undergoing SCT, occurring in 30–39% of cases.5,8 They may be of infectious, cerebrovascular, toxic, immunemediated, or metabolic origin.9 Several drugs routinely used during SCT have also been associated with neurological abnormalities, for example, cyclosporin A used alone or in combination with other agents, such as methylprednisolone and ganciclovir,3 can result in disorientation, an altered mental status, visual disturbance, and coma. However, WE should also be considered as a possible cause of neurological manifestations in specific situations after transplantation. Patients receiving long-term TPN and glucose-containing i.v. solutions require larger amounts of thiamine to metabolize their carbohydrate intake, which can rapidly deplete thiamine stores. A previous study showed that a state of depletion could develop within 18–20 days in patients receiving a strict thiamine-free diet.10 In the current case, the deficiency was clinically noted from day þ 27.
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Thiamine was not included in the commercial TPN products used in this case, and the likelihood of the vitamin components of the commercial TPN products and postSCT situation accelerating the depletion of thiamine stores was overlooked. Not all patients who received the commercial TPN products developed WE, possibly due to receiving multivitamin products containing thiamine for other reasons or to eating food even during conditioning. In conclusion, although WE is an unusual complication of SCT, prolonged TPN without the addition of thiamine can certainly cause WE; therefore, the addition of thiamine in the form of i.v. multivitamins is necessary. JH Baek1 SK Sohn1,2 DH Kim1 JG Kim1,2 HW Lee3 SP Park3 KB Lee1,2
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Department of Hematology/ Oncology, Kyungpook National University Hospital, Daegu, Korea; 2 Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea; and 3 Department of Neurology, Kyungpook National University Hospital, Daegu, Korea
References 1 Sullivan KM. Complications of bone marrow transplantation. In: Hoffman R, Benz Jr EJ, Shattil SJ et al (eds).
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