Case report

Abstract

Rationale:Central nervous system (CNS) involvement of graft versus host disease (GvHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic CNS GvHD symptoms are heterogeneous and include cerebrovascular manifestations, demyelinating disease and immune-mediated encephalitis. CNS-Acute GvHD is not formally defined in literature.Patients concerns and diagnoses:We report 7 cases of CNS-GvHD among which two had histological-proven disease. We reviewed 32 additional cases of CNS GvHD published in literature since 1990. In this cohort, 34 patients were transplanted for hematologic malignancies, and 5 for non-malignant hematopoiesis disorders. Of these patients, 25 had a history of chronic GvHD and immunosuppressive treatment had been decreased or discontinued in 14 patients before neurological symptoms onset. Median neurological disorder onset was 385 days [7-7320]. Patients had stroke-like episodes (n = 7), lacunar syndromes (n = 3), multiple sclerosis-like presentations (n = 7), acute demyelinating encephalomyelitis-like symptoms (n = 4), encephalitis (n = 14), mass syndrome (n = 1), and 3 had non-specific symptoms. Median neurological symptoms onset was 81.5 days [7-1095] for patients without chronic GVHD history versus 549 days [11-7300] for patients with chronic GVHD (P = 0.001). Patients with early involvement of CNS after allo-HSCT and no chronic GVHD symptoms were more frequently suffering from encephalitis (64% versus 28%, P = 0.07), whereas stroke-like episodes and lacunar symptoms were less frequent (9% versus 36%, P = 0.13).Interventions:34 patients with CNS-GvHD were treated with immunosuppressive therapy, including corticosteroids for 31 of them. Other treatments were intravenous immunoglobulin, plasmapheresis, cyclophosphamide, calcineurin inhibitors, mycophenolic acid, methotrexate and etoposide.Outcomes:27 patients achieved a response: 10 complete responses, 15 partial responses and 2 transient responses. Of 25 patients with sufficient follow-up, 7 were alive and 18 patients deceased after CNS-GvHD diagnosis.Lessons:CNS-related GvHD is a rare cause of CNS disorders after allo-HSCT and is associated with a poor prognosis.

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

“…Moreover, the whole clinical spectrum of the entity has not yet been fully described. Previous reports have suggested that CNS-GVHD can present with three main clinico-pathological manifestations: immune-mediated vasculitis, immune-mediated demyelinating lesions and immunemediated encephalitis (Campbell and Morris, 2005;Delios et al, 2012;Grauer et al, 2010;Harvey et al, 2014;Maffini et al, 2017;Padovan et al, 1999;Ruggiu et al, 2017;Saad et al, 2009;Tomonari et al, 2003). Here, we report a case of CNS-GVHD presenting as an ingravescent encephalopathy, without any significant lesion on MRI but with diffuse alteration of brain activity on 18F-FDG PET-CT imaging.…”

“…Historically, it was considered that the CNS could not be affected by GVHD. However, over the last decade, preclinical data (Belle et al, 2017;Hartrampf et al, 2013;Sostak et al, 2004) and clinical case reports (Harvey et al, 2014;Openshaw et al, 1995;Sostak et al, 2010;Stefanou and Bischof, 2017;Voss and Bischof, 2010) progressively accumulated and CNS-GVHD is now becoming recognized as a true entity (Armstrong et al, 1997;Belle et al, 2017;Grauer et al, 2010;Hartrampf et al, 2013;Harvey et al, 2014;Maffini et al, 2017;Openshaw et al, 1995;Rouah et al, 1988;Ruggiu et al, 2017;Sostak et al, 2004;Sostak et al, 2010;Stefanou and Bischof, 2017;Voss and Bischof, 2010). Nevertheless, the diagnosis of CNS-GVHD still remains difficult mainly because of the low prevalence of the disease, confounding factors and heterogeneous clinical presentations.…”

“…Progression to chronic form may theoretically affect any organ and is characterized by clinical manifestations resembling those observed in autoimmune disorders (Jagasia et al, 2015, Pechey et al, 2015, Terada et al, 2017. Few cases of GVHD of the central nervous system (CNS-GVHD) have been reported so far (Ruggiu et al, 2017). However, it is not excluded that this complication is underdiagnosed (Armstrong et al, 1997;Rouah et al, 1988).…”

A Case of Multiple Sclerosis—Like Relapsing Remitting Encephalomyelitis Following Allogeneic Hematopoietic Stem Cell Transplantation and a Review of the Published Literature

“…GvHD rarely affects the CNS, but when it is involved there is often a significant systemic GvHD elsewhere (4). Patients with chronic GvHD affecting the CNS may present with stroke-like episodes, transverse myelitis, multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM) like disorders, encephalitis, and other nonspecific neurological symptoms (5).…”

“…Secondary autoimmune diseases, particularly thyroid and other endocrine disorders are recognized complications following allogeneic HSCT, but MS-like presentation has rarely been reported in the literature (5)(6)(7)(8). In some cases, there is apparent adoptive transfer of specific autoimmune diseases or autoimmune diathesis (9).…”