Non-traumatic Rectus Sheath Hematoma During Direct Oral Anticoagulation.

We report a case of anticoagulation therapy complicated by a non-traumatic rectus sheath hematoma (RSH). RSH is a relatively rare occurrence caused by bleeding into the rectus sheath following the rupture of the superior and inferior epigastric vessels combined with a primary tear of the rectus muscle fibers. Herein, we report a rare presentation of RSH in a 73-year-old man taking the direct oral anticoagulant (DOAC) apixaban orally. The patient presented with sudden right abdominal pain after a severe cough, which worsened with cough and movement. The Fothergill and Carnett signs were positive. The platelet count, renal function test, and the prothrombin time/international normalized ratio were within the normal range. The activated partial thromboplastin time was 40.0 s, slightly longer than normal. Computed tomography (CT) of the abdomen and pelvis showed RSH, and DOAC therapy was temporarily discontinued. Subsequently, RSH resolution was confirmed via CT four weeks after the onset. DOACs are safer and more efficacious than warfarin for patients with non-valvular atrial fibrillation. However, RSH is a potential complication of anticoagulant therapy. This case report demonstrates that RSH should be considered in the differential diagnosis of sudden-onset abdominal pain and mass in patients on DOACs.

[Cytomegalovirus associated myelitis in a non-immunocompromised adult due to initial cytomegalovirus infection].

The patient was a 30-year-old man who developed muscle weakness in both lower extremities, sensory deficits below the fourth thoracic spinal cord level, and bladder rectal dysfunction owing to cytomegalovirus (CMV) associated myelitis. His blood tests showed mononucleosis, hepatic dysfunction, and the presence of serum CMV-IgM antibodies, and T2-weighted imaging on MRI displayed a continuous high signal on the ventral side of the spinal cord. Although his medical history and laboratory tests did not indicate that he was immunocompromised, we speculated he had CMV-associated myelitis. As the first infection with CMV in a non-immunocompromised adult can result in mononucleosis, we considered that this patient developed myelitis after mononucleosis caused by CMV infection for the first time. CMV-associated myelitis in non-immunocompromised individuals is rare. In general, CMV infections are common in immunosuppressed individuals. However, in Japan, adults with CMV antibodies have recently been decreasing, and hence CMV infections in non-immunocompromised adults are expected to increase in the future.

Characteristics of sagittal spinopelvic alignment in patients with Parkinson's disease.

INTRODUCTION: The aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD). METHODS: The study included patients with idiopathic PD (aged <80 years and with abnormal posture). All patients underwent whole-spine lateral and coronal radiography. Sagittal spinopelvic alignment was evaluated using nine parameters. Motor symptoms were evaluated using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score-with bradykinesia and axial motor sub-scores. Multivariate analysis was used to analyze associations between motor symptoms and sagittal spinopelvic alignment in PD patients according to sex. RESULTS: The study subjects were 79 PD patients (39 men, 40 women; median age, 70 years). Clear sex-related differences were noted. In male patients, the MDS-UPDRS part III score correlated significantly with cervical sagittal vertical axis (SVA), and bradykinesia and axial motor scores correlated significantly with SVA, cervical SVA, and T1 slope. In female patients, the MDS-UPDRS part III score correlated significantly with thoracic kyphosis, bradykinesia score correlated significantly with cervical SVA and thoracic kyphosis, and the axial motor score correlated significantly with SVA, cervical SVA, T1 slope, sacral slope, and pelvic tilt. CONCLUSION: Our results showed clear correlations among various motor symptoms and sagittal global alignment in PD patients and that these correlations are different in female PD patients and their male counterparts.

[Posterior reversible encephalopathy syndrome during intravenous immunoglobulin therapy in Guillain-Barré syndrome].

A 63-year-old woman was diagnosed with Guillain-Barré syndrome (GBS), and intravenous immunoglobulin (IVIg) therapy was initiated. On the second day of IVIg therapy, she became less alert (JCS III-200) and had hyponatremia. Brain MRI showed vasogenic edema in bilateral occipital lobes, which disappeared afterwards. Her clinical course and MRI findings were consistent with those of posterior reversible encephalopathy syndrome (PRES). As a result of considering the timing of the onset of GBS and PRES and the degree of hyponatremia and hypertension in some documented patients, the cause of PRES onset in this case is considered to be IVIg therapy itself and IVIg therapy-induced hyponatremia.

Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients.

Myasthenia gravis (MG) is an autoimmune disorder generally mediated by antibodies against the acetylcholine receptors (AChR) of the skeletal muscles. CD4 T cells help B cells to produce antibodies through their production of cytokines or chemokines. In this study, we evaluated the frequency of regulatory (Treg) and IL-17 producing CD4 T-cell subsets (Th17) in peripheral blood mononuclear cells (PBMCs) of patients with MG. The transcription factor, forkhead transcription factor (Foxp3), is essential for T-cell regulatory function, and the orphan nuclear receptor, RORgammaT, is important in Th17 cell differentiation. In MG patients, Foxp3 mRNA expression in PBMCs was lower than those in healthy subjects (p=0.007), while there was no significant difference of RORgammaT mRNA expression between MG patients and healthy subjects. Glucocorticoid-induced tumour-necrosis-factor receptor-related protein (GITR) is expressed predominantly on CD4(+)CD25(+) Treg cells. We found that the number of GITR(+)CD4(+)CD25(+) T cells in peripheral lymphocytes in MG patients was lower than that in healthy subjects (P<0.01). In addition, there was a significant positive correlation between the change of the frequency of GITR(+)CD4(+)CD25(+) T cells and the changing rate in quantitative myasthenia gravis scores (%) (p=0.03). Furthermore, there was a significant negative correlation between the change of the percentage of GITR(+)CD4(+)CD25(+) T cells (% lymphocytes) and the changing rate of daily PSL doses (%) (P=0.002). The relative RORgammaT levels in PBMCs negatively correlated with the Th1/Th2 ratio in CD4(+) cells in MG patients (p=0.014). In conclusion, our findings suggest that Th17 cells affect the production of autoantibodies through their influence on the Th1- and Th2-cytokine balance in PBMCs of MG patients. On the other hand, Treg cells are suggested to be involved in the clinical condition or severity of MG disease.

Clinical implications of the type 1/type 2 balance of helper T cells and P-glycoprotein function in peripheral T lymphocytes of myasthenia gravis patients.

Myasthenia gravis is an autoimmune disorder mediated by antibodies against the acetylcholine receptors of the skeletal muscles. Imbalances between T helper type 1 and type 2 cytokine production play a key role in the induction and development of several autoimmune diseases. Peripheral T helper type 1 and type 2 cells in 50 myasthenia gravis patients were estimated by intracellular cytokines. The percentage of T helper type 1 cells in CD4(+) cells was higher than that of type 2 or type 0 cells (P<0.0001). There was a significant correlation between T helper type 1/type 2 ratio and the P-glycoprotein function on CD3(+) T cells (P=0.008). In the patients treated with prednisolone alone (n=12), there was a significant correlation negatively between the percentage of change in the T helper type 1/type 2 ratio and the reduction rate of quantitative myasthenia gravis scores after 12 months of treatment (P=0.012). In contrast, all of the patients treated with prednisolone and calcineurin inhibitor in combination saw reductions in the scores. Our data suggest that the T helper type 1/type 2 ratio was involved in the disease activity of the patients treated with prednisolone alone. On the other hand, the patients treated with prednisolone and calcineurin inhibitor in combination had their disease condition improved regardless of the T helper type 1 predominance. Therefore, the data suggest that supplemental calcineurin inhibitors are effective for the myasthenia gravis patients treated with prednisolone alone when their T helper balance shifts toward to type 1.

P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis patients: clinical implications and influence of glucocorticoid administration.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with a chronic clinical course that requires long-term glucocorticoid (GC) therapy. A drug efflux pump, P-glycoprotein (P-gp), actively transports GC out of target cells, thereby reducing its efficacy. We evaluated the P-gp function of peripheral-blood mononuclear cells in 59 MG patients. P-gp function was estimated from a decrease in fluorescent P-gp substrate Rhodamine 123 and its inhibition by the conformation-sensitive UIC2 monoclonal antibody. P-gp function on CD8(+) T cells in 21 MG patients having experienced GC therapy was higher than that in 19 MG patients having no history of GC therapy (p=0.026). There was a significant correlation between P-gp function in CD3(+) (r=0.55, p=0.014) or CD4(+) (r=0.48, p=0.034) T cells and the total dose of prednisolone for treatment. P-gp function on CD4(+) T cells in MG patients who showed low responses to prednisolone therapy (n=8) was higher than that in patients who showed relatively high responses to prednisolone therapy (n=10) (p=0.045). These results suggest that higher P-glycoprotein activity on CD3(+) or CD4(+) cells necessitated treatment with higher steroid doses in order to achieve a clinical response. The measurement of P-gp function on CD4(+) T cells is useful in the assessment of clinical response to GC therapy.