Neuronal surface antibody-mediated encephalopathy as manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Abstract

Although it remained controversial for a long time, central nervous system (CNS) involvement of graft-versus-host disease (GVHD) is now becoming recognized as a real nosological entity. Previous case reports have suggested heterogeneous clinical presentations and it is not excluded that the whole spectrum of manifestations has not yet been fully described. Here, we report the case of a 58-year-old man with chronic GVHD who developed a rapidly ingravescent encephalopathy. There was no evidence for CNS immune-mediated lesions on conventional imaging nor for cellular infiltration in the cerebrospinal fluid. Serum analyses revealed the presence of anti-neuronal antibodies directed against anti-contactin-associated protein 2 (anti-Caspr2), a protein associated with voltage-gated potassium neuronal channels. Functional imaging with 2-deoxy-2-[fluorine-18] fluoro- d-glucose integrated with computed tomography (18F-FDG PET-CT) demonstrated diffuse cortical and subcortical hypometabolism. The patient was treated with a combination of immunosuppressive agents (corticosteroids, cyclophosphamide and rituximab) and progressively recovered normal neurocognitive functions. Taken together, these data suggest that CNS-GVHD may manifest as a reversible antibody-mediated functional encephalopathy. This report suggests for the first time the interest of screening for anti-neuronal antibodies and functional imaging with brain 18F-FDG PET-CT in diagnosing this severe complication of allogeneic hematopoietic cell transplantation (alloHSCT).

Stem Cell Therapy in Neuroimmunological Diseases and Its Potential Neuroimmunological Complications

“…Reported were patients with acute demyelinating encephalomyelitis (ADEM) and ADEM-like syndromes ( n = 7), immune-mediated encephalitis ( n = 5, one each with N -methyl- d -aspartate-receptor (NMDAR), glutamate-decarboxylase (GAD), leucine-rich, glioma inactivated 1 (LGI1) and GAD, and contactin-associated-protein 2 (CASPR2) antibodies), immune-mediated myelopathy ( n = 15, one with MOGAD, and one with AQP4 antibody-negative NMOSD with fulfillment of the diagnostic criteria, 13 with seronegative myelopathies; three had additional optic neuritis), MS ( n = 3), and bilateral optic neuritis ( n = 1) [ 23 , 136 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 ].…”

“…Stem-cell therapies were offered as a treatment option due to malignant diseases (leukemia, lymphoma, myelodysplastic syndrome, and pineoblastoma) in most cases and rarely due to autoimmune-mediated diseases (one each for MS, myelitis, and CIDP) [ 23 , 136 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 ]. Hematopoietic stem cells of different origin (allogeneic n = 26, autologous n = 1, and not described n = 1) were infused in all but two patients [ 23 , 136 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 ]. In these two patients, allogeneic umbilical cord blood-derived mesenchymal stem cells and autologous bone marrow-derived mesenchymal stem cells (myelitis) were applied for the treatment of autoimmune-mediated diseases [ 189 , 190 ].…”

Hematopoietic Stem Cell Transplantation for Neurological Disorders: A Focus on Inborn Errors of Metabolism

“…Notably, secondary neuro-immune complications like the recently recognized encephalitides associated with neuronal cell-surface protein antibodies can develop due to aberrant immune reconstitution after Allo-HSCT. This may in turn, lead to a further increased management complexity ( Pirotte et al, 2018 ; Nagai et al, 2019 ; Hümmert et al, 2021 ).…”

Standard treatment–refractory cytomegalovirus encephalitis unmasked by immune reconstitution inflammatory syndrome and successfully treated with virus‐specific hyperimmune globulin

“…Cerebral toxoplasmosis and fungal brain abscess were ruled out because of negative microbiological and radiological assessments. Leukaemia relapse was excluded by flow cytometry analysis, while a CNS‐GVHD was highly unlikely because no other organs were involved 8–10 …”

“…Leukaemia relapse was excluded by flow cytometry analysis, while a CNS-GVHD was highly unlikely because no other organs were involved. [8][9][10] Immune reconstitution inflammatory syndrome is a clinical entity related to the immune system's restoration, which follows immunosuppression after allogeneic HSCT, presenting as the unmasking of a clinically silent infection or as the worsening clinical manifestations of a pre-existing infection. 11 It should be ruled out in allogeneic HSCT recipients with neurological symptoms.…”