Transient global amnesia and hippocampal diffusion restriction: an overlooked radiological finding.

Transient global amnesia (TGA) is characterized by isolated sudden anterograde amnesia. Diffusion restriction can be observed in the hippocampus on DWI-MRI at varying rates in TGA patients. This study analyzes the prevalence and characteristics of the hippocampal diffusion restriction (HDR), its relationship with vascular risk factors, and the prevalence of lesions overlooked in routine reports. 91 patients diagnosed with TGA at a tertiary hospital between 2011 and 2022 were evaluated retrospectively. The mean age was 64.8 ± 7.3 years, and 63.7% of patients were female. 75.8% of the patients had at least one vascular risk factor. Focal diffusion restriction was detected in 17 patients (18.5%) on DWI-MRI, with only one being extra-hippocampal. 81.2% of HDR was detected when DWI-MRI scan was performed between 12 and 96 h after the onset of symptoms. HDR was detected most when the imaging was performed in 24 to 48 h (p = 0.03). There was no correlation between the duration of symptoms and the detection rates of HDR (p = 0.55). In 9 patients (53% of 17) diffusion restriction was not specified in routine radiology reports. Although focal ischemia, venous flow abnormalities, migraine and epileptic phenomena have been suggested in its etiology, TGA is a clinical condition of which pathophysiology has not been determined clearly. Signal changes observed in DWI-MRI has led to discussions that cerebrovascular etiology may play a role, yet more comprehensive studies are required to prevent and manage TGA. HDRs can be overlooked in routine reports. Therefore, the DWI-MRI images of patients with TGA should be examined vigilantly.

Alterations in Hematopoietic and Mesenchymal Stromal Cell Components of the Osteopetrotic Bone Marrow Niche.

Osteopetrosis is a rare inherited disease characterized by impaired osteoclast activity causing defective bone resorption and bone marrow aplasia. It is fatal in early childhood unless hematopoietic stem cell transplantation is performed. But, the transplant course is complicated with engraftment failure. Recently, osteoclasts have been described as the potential regulators of hematopoietic stem cell (HSC) niche. Here we investigated the alterations in the HSC and mesenchymal stromal cell (MSC) components of osteopetrotic niche and their interactions to mimic the stem cell dynamics/trafficking in the BM niche after HSC transplantation. Induced pluripotent stem cells were generated from peripheral blood mononuclear cells of patients with osteopetrosis carrying TCIRG1 mutation. iPSC lines were differentiated into hematopoietic and myeloid progenitors, then into osteoclasts using a step-wise protocol. We first demonstrated a shift toward monocyte-macrophages lineage regarding hematopoietic differentiation potential of osteopetrotic iPSC-derived hematopoietic progenitors (HPCs) and phenotypically normal and functionally defective osteoclast formation. The expression of the genes involved in HSC homing and maintenance (Sdf-1, Jagged-1, Kit-L, and Opn) in osteopetrotic MSCs recovered significantly after coculture with healthy HPCs. Similarly, the restoration of phenotype, impaired differentiation, and migratory potential of osteopetrotic iHPCs were observed upon interaction with healthy MSCs. Our results establish significant alterations in both MSC and HPC compartments of the osteopetrotic niche, and support the impact of functionally impaired osteoclasts in defective niche formation.

Association of Pre-Transplant Angiopoietin-2 Index with the Risk of Acute Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

Objective: Angiogenic factors (AFs) released under endothelial stress are reflective of tissue healing, while some may also contribute to tissue damage/inflammation. We investigated whether alterations in the pre-transplant levels of AFs were associated with the risk of acute graft-versus-host disease (aGvHD). Materials and Methods: The pre-conditioning plasma levels of angiopoietin-2 (Ang2), endoglin, and follistatin were measured for 37 patients together with inflammatory markers. The index values defined were evaluated to better identify the alterations. Results: The patients had higher pre-conditioning levels of Ang2, endoglin, and follistatin compared to controls. The patients with aGvHD had higher Ang2 index and lower albumin index scores in comparison to those without aGvHD. Multivariate analysis revealed that the pre-transplant Ang2 index was an independent risk factor for aGvHD development. Conclusion: Pre-transplant evaluation of plasma Ang2 levels along with inflammatory status even before conditioning is associated with endothelial vulnerability. The pre-transplant Ang2 index could be a promising candidate to estimate the risk of aGvHD.