Hindawi Case Reports in Immunology Volume 2022, Article ID 4174755, 4 pages https://doi.org/10.1155/2022/4174755 Case Report Limbic Encephalitis following Allogeneic Hematopoietic Stem Cell Transplantation 1 2,3 3,4 4 Silje Johansen , Jostein Kra˚kenes, C. A. Vedeler , Anette Margrethe Storstein, 5,6 and Ha˚kon Reikvam Department of Medicine, Haraldsplass Deaconess Hospital, N-5021 Bergen, Bergen, Norway Department of Radiology, Haukeland University Hospital, N-5021 Bergen, Norway Department of Clinical Medicine, University of Bergen, N-5021 Bergen, Norway Department of Neurology, Haukeland University Hospital, N-5021 Bergen, Norway Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Bergen, Norway Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway Correspondence should be addressed to Ha˚kon Reikvam; email@example.com Received 22 March 2022; Revised 5 July 2022; Accepted 18 August 2022; Published 10 September 2022 Academic Editor: Christian Drouet Copyright © 2022 Silje Johansen et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A woman with myelodysplastic syndrome (MDS) was treated with allogeneic hematopoietic stem cell transplantation (allo- HSCT). 65 days after the transplantation, she developed fatigue and central neurological symptoms. Clinical workup including magnetic resonance imaging (MRI) and cerebrospinal Œuid (CSF) examination revealed ’ndings suspicious for limbic en- cephalitis (LE), successfully treated with intravenous immunoglobulins and intravenous corticosteroids. Although a rare complication after allo-HSCT, physicians should be aware of neurological symptoms that develop throughout the transplantation course. initially treated with 5-azacitidine, while preparing for an allo- 1. Introduction HSCT. Allo-HSCT was performed with reduced intensity e use of allogeneic hematopoietic stem cell transplantation conditioning (RIC) regimen with Œudarabine, treosulfan, and (allo-HSCT) is increasing in most countries , since this anti-thymocyte globulin (ATG), before transplant with a treatment is becoming more reliable and more accessible. e matched unrelated donor (MUD), with both recipient and treatment, on the other hand, is associated with a relatively donor being positive for Epstein–Barr virus (EBV) and cy- high incidence of serious, and in worst case fatal, complica- tomegalovirus (CMV) IgG. She received cyclosporine A from tions. Furthermore, neurological complications are rare, but a the day before allo-HSCT and methotrexate the 1st, 3rd, and dreaded complication of allo-HSCT . Reports support that a 6th day after allo-HSCT as prophylaxis towards graft versus persistent neurological impairment occurs in many of those host disease(GvHD). Already at day +21, she developed a patients who su–er from neurological complications after allo- generalized exanthema diagnosed as toxic epidermal necrolysis HSCT . Herein, we present a patient who developed a se- treated with intravenous immunoglobulin (IVIG) and meth- rious neurological complication after allo-HSCT. ylprednisolone. e biopsy of the skin showed no signs of GvHD. She had a late engraftment, but at day +28, she had trilinear hematopoiesis and 99% donor chimerism and she 2. Case Presentation showed no signs of acute GvHD (aGvHD). However, by day A 49-year-old previously healthy woman, with no history of +65, she developed fatigue and altered mental level with confusion and seizures. She had low fever but normal C-re- mental illness or neurological abnormalities, was diagnosed with myelodysplastic syndrome (MDS) with ’brosis. She was active protein (CRP). e seizures were dominated by 2 Case Reports in Immunology Figure 1: (a–c) Coronal FLAIR-MRI scan reveals slight enlargement and increased signal intensity of the amygdala and hippocampus bilaterally. Table 1: All autoantibodies tested in serum and spinal ﬂuid in our patient (all were below reference values). Anti LGI 1, anti CASPR2, anti gaba R b1/2, anti DPPX, anti-GluR type AMPA½, anti Onconeuronal and encephalitis autoantibodies in GluR type NMDA, anti Tr, anti Zic4, anti GAD 65, antiSOX1, anti Ma2, antiMa1, anti spinal ﬂuid CRMP5, anti Amphiphy, anti Yo, anti Ri, anti Hu Anti LGI 1, anti CASPR 2, anti gaba R b1/2, anti DPPX, anti-GluR type AMPA ½, anti Onconeuronal and encephalitis autoantibodies in GluR type NMDA, anti MOG, aquaporin, anti Tr, anti Zic4, anti GAD 65, antiSOX1, serum anti Ma2, antiMa1, anti CRMP5, anti amphiphy, anti Yo, anti Ri, anti Hu Antinuclear antibodies and antineutrophil SM Ig G, RNP Ig G, SS-A Ig G, SS-B Ig G, Jo1IgG, Scl-70 Ig G, Centromer Ig G, cytoplasmic antibodies in serum dsDNA Ig G, anti -CRT, ribosomal P Ig G, SM RNP Ig g, anti Pr 3, Anti-MPO contractions lasting only seconds in face, neck, arm, and leg. symptoms, and seizures, combined with MRI ﬁndings of However, an electroencephalogram (EEG) did not show sei- temporal lobe involvement, and CSF inﬂammatory abnor- zure. Magnetic resonance imaging (MRI) demonstrated bi- malities including detection of autoantibodies . Our pa- laterally increased signal intensity of the amygdala and tient headlights the possibility of this rare complication post hippocampus (Figures 1(a)–1(c)). Investigation of the cere- allo-HSCTand is a reminder that detection of autoantibodies brospinal ﬂuid (CSF) revealed increased number of leukocytes, in the CSF is not a prerequisite for the diagnosis of LE. 42 ×10 /L (reference<3), mononuclear pleocytosis, increased Subacute development of short-term memory deﬁcits is often protein level 1.93g/L (reference 0.15–0.50), and serum like IgG typical for LE, although it was probably overlooked in the bands in isoelectric focusing of CSF. She was initially treated present case by other symptoms such as headache, irritability, with broad-spectrum antibiotic and antiviral intravenous sleep disturbance, delusions, hallucinations, and seizures . treatment, but these were discontinued as investigations for *ermal sensations, piloerection, and paroxysmal dizziness underlying viral or bacterial causes were negative, including might be symptoms resulting from focal seizure activity in LE human herpes virus-6 (HHV-6) in cerebrospinal ﬂuid. Fur- . Faciobrachial dystonic seizures are especially helpful diagnostically as they are nearly pathognomonic in a subtype thermore, as demonstrated in Table 1, 17 diﬀerent standard onconeural and encephalitis autoantibodies were not detected of LE. A normal EEG during seizures should not eliminate the in serum or CSF and antinuclear antibodies were not detected diagnosis, as coincident epileptiform discharges are seen only in serum. A computer tomography (CT) scan with intravenous in the minority [4, 5]. Our patient did not have an EEG with contrast of the thoracic, abdominal, and pelvic regions had typical ﬁndings that could correlate to the seizure, but an EEG recently been performed with no signs of other malignancy. with generalized low frequency activity supporting a diﬀuse *e clinical and radiological presentation were considered to central nerve system dysfunction. be an autoimmune limbic encephalitis (LE) following allo- LE is an inﬂammatory disease involving the mesial tem- HSCT, due to cognitive impairment, seizures, MRI ﬁndings, poral lobes and the limbic structures, amygdala, and hippo- and pleocytosis in the CSF. Accordingly, she was treated with campus. MRI often reveals abnormal high signal intensity on intravenous corticosteroids, methylprednisolone 1000mg for 5 FLAIR and T2 weighted images in the mesial temporal lobes . Typical MRI signal was found in our case. However, days, and intravenous immunoglobulins for 5 days, total of 2g/ kg. She had an initial improvement, but the symptoms relapsed sometimes MRI may be normal, and in such cases, 18-ﬂuo- after 15 days, and the treatment was repeated and supple- rodeoxyglucose (18F-FDG) PET imaging has been reported to mented with tapering dose of per oral prednisolone for several typically reveal mesial temporal lobe hypermetabolism . weeks. *e patient’s symptoms went slowly in regression, and Post-transplant acute/subacute LE has been described as control MRI after four weeks was normal (Figures 2(a)–2(c)). a complication of allo-HSCT, occurring relatively early in the post-transplant period. Risk factors have been identiﬁed as heavily pretreating conditioning including ATG and 3. Discussion corticosteroids treatment . *e classical presentation and clinical ﬁndings of LE include Neurological complications after allo-HSCT can be clas- rapidly progressive short-term memory loss, psychiatric siﬁed according to etiology or clinical presentation as listed in Case Reports in Immunology 3 Figure 2: (a–c) Coronal FLAIR-MRI scan after treatment, four weeks later, was normal. Table 2: Neurological complication seen after allogeneic hematopoietic stem cell transplantation. Drug-related Metabolic Infectious Cerebrovascular Classiﬁed neurological complications based on etiology Immune/inﬂammatory CNS relapse of underlying disease Secondary CNS malignancy Undeﬁned Focal epileptic seizure or general epileptic seizure Cranial neuropathy PRES Encephalopathy PML Meningoencephalitis or encephalitis Meningitis (leukemic, infectious), cerebritis, or ventriculitis Autoimmune encephalitis Classiﬁed central nervous system neurological complications based on clinical PALE disease ADEM LETM Optic neuritis Short myelitis Subarachnoid hemorrhage TA-TMA TIA NHL relapse CNS-PTLD Cognitive impairment PRES, posterior reversible encephalopathy syndrome, PALE, post-transplant acute limbic encephalitis, PML, progressive multifocal leukoencephalopathy, TA-TMA, transplant-associated thrombotic microangiopathy, TIA, transient ischemic attack, ADEM, acute disseminated encephalomyelitis, LETM, longitudinal extensive transverse myelitis, CNS-PTLD, central nervous system EBV-related post-transplant lymphoproliferative disorder, and NHL, non- Hodgkin lymphoma. Table 2 . *e etiology of LE could be divided in infectious herein limbic encephalitis, could anticipate speciﬁc treatments and non-infectious causes, where the former often has been and inﬂuence the rate or the extent of long-term disabilities . related to HHV-6 reactivation . However, without evidence of infectious origin, immunological mechanisms should be Data Availability considered. When ﬁrst-line therapy with steroids, immuno- globulins, and/or plasma exchange fails, one converts to sec- No data were used to support this study. ond-line immunotherapy. Second-line immunotherapy includes usually monoclonal antibodies (mAbs) directed at B-cells such as the anti-CD20 antibody rituximab . Our Consent patient responded to corticosteroid and immunoglobulin Written informed consent was obtained from the patent therapy, although it had to repeated. We suggest that a rapid before publication. and circumstantiated diagnosis of autoimmune encephalitis, 4 Case Reports in Immunology Conflicts of Interest *e authors declare that they have no conﬂicts of interest. Acknowledgments *e group’s work related to allo-HSCT research was sup- ported by Helse Vest Rakel and Otto Kristian Bruun’s Fund, Øyvinn Mølbach-Pedersens Fund, Blakstad Maarschalk and Heblings Fund, Rotary International, and Norwegian So- ciety of Internal Medicine. References  J. R. Passweg, H. Baldomero, C. Chabannon et al., “Hema- topoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years,” Bone Marrow Transplantation, vol. 56, no. 7, pp. 1651–1664,  A. O. Dulamea and I. G. Lupescu, “Neurological complica- tions of hematopoietic cell transplantation in children and adults,” Neural Regeneration Research, vol. 13, no. 6, pp. 945–954, 2018.  M. Wieczorek, S. Mariotto, S. 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Case Reports in Immunology
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Published: Sep 10, 2022