A Case Report of Central Nervous System Graft-Versus-Host Disease and Literature Review

Li, Mingming; Zhang, Yue; Guan, Yujia; Zhang, Zunwei; Dong, Hanbing; Yang, Zhao; Deng, Hui

doi:10.3389/fneur.2021.621392

Cited by 10 publications

(13 citation statements)

References 51 publications

(53 reference statements)

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“…The clinical picture of acute GVHD is often connected to neurological deficits in patients, morphological CNS white matter changes detectable by magnetic resonance imaging and intraparenchymal lymphocytic infiltration of the brain upon autopsy ( 31 , 32 ). In line with the findings, studies also reported neurological deficits including drowsiness, dysphoria, right dazedness and MRI findings of abnormal cerebra gyrus swelling, corpus signal, diffused white matter regions ( 33 ). Biopsy studies on GVHD brains showed axonal depletion representative of demyelination disease in a patient.…”

Section: Human Studies On Cns-gvhdsupporting

confidence: 64%

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

Vinnakota

Zeiser

2021

Front. Immunol.

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Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for patients with hematological malignancies. Acute Graft versus host diseases (GVHD) is a major immune mediated side effect of allo-HCT that can affect the central nervous system (CNS) in addition to post-allo-HCT vascular events, drug toxicity or infections. Here we summarize and discuss recent preclinical data on the CNS as a target of acute GVHD and the known mechanisms contributing to neurotoxicity with a focus on microglia and T cells. We also discuss open questions in the field and place the findings made in mouse models in a clinical context. While in mice the neurological deficits can be assessed in a controlled fashion, in patients the etiology of the CNS damage is difficult to attribute to acute GVHD versus infections, vascular events, and drug-induced toxicity. Ultimately, we discuss novel therapies for GVHD of the CNS. Our understanding of the biological mechanisms that lead to neurotoxicity after allo-HCT increased over the last decade. This review provides insights into CNS manifestations of GVHD versus other etiologies of CNS damage in mice and patients.

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Section: Human Studies On Cns-gvhdsupporting

confidence: 64%

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

Vinnakota

Zeiser

2021

Front. Immunol.

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“…Furthermore, oligoclonal bands and the improvement of symptoms after immunosuppressive treatment supported the diagnosis of CNS-GVHD. Li et al [ 6 ] found that lymphocytic vasculitis has a prominent position in the existing CNS-GVHD histological data, so we speculated that the white matter lesions of the patient was caused by vasculitis involving small vessels associated with CNS-GVHD after excluding other causes.…”

Section: Discussionmentioning

confidence: 91%

“…Chronic GVHD occurs in 30% to 50% of transplant patients from related donors, [ 3 ] but neurological complications are rare and 47 cases of CNS-GVHD have been reported so far which presented with stroke-like episodes or lacunar syndrome, acute disseminated encephalomyelitis or multiple sclerosis like presentation, encephalopathy or encephalitis and other atypical symptoms. [ 6 ]…”

Section: Discussionmentioning

confidence: 99%

“…Previous cases with biopsy results revealed CD3, CD4, and CD8 T cells infiltration of perivascular areas. [ 6 ] An experimental mouse model demonstrated parenchymal lymphocytic inflammation, microglia activation, and mild cerebral angiitis after allo-HSCT. [ 9 ] Therefore, inflammatory cells infiltration owing to chronic GVHD may promote arterial remodeling and pathological characteristics could be crucial for the diagnose of cerebral vasculitis.…”

Section: Discussionmentioning

confidence: 99%

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Cerebral large artery occlusion in chronic graft-versus-host disease

Gao

Sun

et al. 2021

Medicine

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Rationale: Cerebral large artery occlusion in chronic central nervous system graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was very scarce. We described a young patient with bilateral white matter lesions and symptomatic internal carotid artery occlusion after allo-HSCT with the history of aplastic anemia. Patient concerns: A 17-year-old girl with the history of aplastic anemia developed recurrent headache and sudden hemiplegia of right limbs 2 years after allo-HSCT. Diagnoses: She was diagnosed with skin chronic graft-versus-host disease 19 months after allo-HSCT. Brain magnetic resonance imaging showed bilateral subcortical white matter abnormal signals and hyperintensity of left fronto-parietal lobe on diffusion weighted imaging and corresponding hypointense apparent diffusion coefficients indicating acute infarction. CT angiography revealed thrombosis in left internal carotid artery. Carotid plaque high-resolution magnetic resonance imaging showed annular enhancement of vascular wall revealing signs of vasculitis. Interventions: Intravenous immunoglobulin, methylprednisolone, and anticoagulant therapy were used to treat the patient. Outcomes: The patient's symptoms gradually resolved and she could walk with assistance after 3 weeks before returned home. Lessons: Chronic graft-versus-host disease-associated vasculitis could involve cerebral large vessels which warrants further study.

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“…Reports of CNS GvHD in the literature are rare. A recently published Frontiers case report and literature review ( 112 ) included 46 cases reported between 1990 and 2019. Cases included patients with acute or chronic GvHD prior to or at the time of neurological abnormalities.…”

Section: Acute Neurotoxicity Post Hsctmentioning

confidence: 99%

A Review of Acute and Long-Term Neurological Complications Following Haematopoietic Stem Cell Transplant for Paediatric Acute Lymphoblastic Leukaemia

et al. 2021

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Despite advances in haematopoietic stem cell transplant (HSCT) techniques, the risk of serious side effects and complications still exists. Neurological complications, both acute and long term, are common following HSCT and contribute to significant morbidity and mortality. The aetiology of neurotoxicity includes infections and a wide variety of non-infectious causes such as drug toxicities, metabolic abnormalities, irradiation, vascular and immunologic events and the leukaemia itself. The majority of the literature on this subject is focussed on adults. The impact of the combination of neurotoxic drugs given before and during HSCT, radiotherapy and neurological complications on the developing and vulnerable paediatric and adolescent brain remains unclear. Moreover, the age-related sensitivity of the nervous system to toxic insults is still being investigated. In this article, we review current evidence regarding neurotoxicity following HSCT for acute lymphoblastic leukaemia in childhood. We focus on acute and long-term impacts. Understanding the aetiology and long-term sequelae of neurological complications in children is particularly important in the current era of immunotherapy for acute lymphoblastic leukaemia (such as chimeric antigen receptor T cells and bi-specific T-cell engager antibodies), which have well-known and common neurological side effects and may represent a future treatment modality for at least a fraction of HSCT-recipients.

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A Case Report of Central Nervous System Graft-Versus-Host Disease and Literature Review

Cited by 10 publications

References 51 publications

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

Cerebral large artery occlusion in chronic graft-versus-host disease

A Review of Acute and Long-Term Neurological Complications Following Haematopoietic Stem Cell Transplant for Paediatric Acute Lymphoblastic Leukaemia

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