Small Cortical Infarcts Transformed to Lobar Cerebral Microbleeds: A Case Series

Cerebral microbleeds (MBs) have been often observed due to the development of imaging devices, and are classified to deep and lobar MBs. Lobar MBs are strongly associated with cerebral amyloid angiopathy. Here, we report 3 cases of lobar MBs that developed after small cortical ischemic stroke. One case underwent carotid artery stenting for severe carotid stenosis, one was diagnosed with artery-to-artery embolism, and the other was embolic stroke of undetermined source. New small cortical infarctions were detected with diffusion-weighted magnetic resonance imaging (MRI). Initial MRI revealed no hemorrhage around the ischemic lesion on T2*-weighted gradient-recalled echo or susceptibility-weighted imaging (SWI) at the onset of stroke. Follow-up SWI after 12-20 months revealed lobar MBs in the previously detected ischemic lesions, and high-intensity lesions remained around the MBs on fluid-attenuated inversion recovery imaging. These cases revealed that cerebral MBs developed through the transformation of small cortical infarctions. All cases showed lobar MBs, and these MBs existed in the previously detected ischemic lesions at a chronic stage. Lobar MBs present around ischemic lesions may predict embolic infarcts.     

Two region‐dependent pathways of eosinophilic neuronal death after transient cerebral ischemia

Various types of eosinophilic neurons (ENs) are found in the post‐ischemic brain. We examined the temporal profile of ENs in the core and peripheral regions of the ischemic cortex, and analyzed the relationship to the expression of various cell death‐related factors. Unilateral forebrain ischemia was induced in Mongolian gerbils by transient common carotid artery occlusions, and the brains from 3 h to 2 weeks post‐ischemia were prepared for morphometric and immunohistochemical analysis of ENs. ENs with minimally abnormal nuclei and swollen cell bodies appeared at 3 h in the ischemic core and at 12 h in the periphery. In both locations multiple cell death‐related factors including calcium, µ‐calpain, cathepsin D, 78 kDa glucose‐regulated protein (GRP78) and ubiquitin were activated. In the ischemic core, pyknosis and irregularly atrophic cytoplasm peaked at 12 h, which was associated with significant increases in staining for calcium and µ‐calpain. ENs with pyknosis and scant cytoplasm peaked at 4 days and were positive for TUNEL and calcium staining. In the ischemic periphery, ENs had slightly atrophic cytoplasm and sequentially developed pyknosis, karyorrhexis and karyolysis over 1 week. These cells were positive for TUNEL and calcium staining. All types of EN were negative for caspase 3. There may be two region‐dependent pathways of EN changes in the post‐ischemic brain: pyknosis with cytoplasmic shrinkage in the core, and nuclear disintegration with slightly atrophic cytoplasm in the periphery. This difference coordinates different activation patterns of cell death‐related factors in ENs.     

Treatment outcome of selective digestive decontamination and enteral nutrition in patients with severe acute pancreatitis

Background/Purpose Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP. Methods We divided 90 patients with SAP into three groups: SDD(−)EN(−),group A; SDD(+)EN(−), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C. Results The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN. Conclusions SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.     

Role of Intraoperative Cholangiography in Patients Whose Biliary Tree Was Evaluated Preoperatively by Magnetic Resonance Cholangiopancreatography

Background

Routine performance of intraoperative cholangiography (IOC) during cholecystectomy is controversial. The aim of this study was to evaluate the role of IOC during cholecystectomy in addition to preoperative magnetic resonance cholangiopancreatography (MRCP) in our institution over a 12-year period.

Methods

A total of 425 consecutive patients who underwent IOC during cholecystectomy were included in this study. MRCP was performed preoperatively for bile duct evaluation in all patients. When common bile duct (CBD) stones were detected, they were removed endoscopically before the operation. We estimated the results of IOC in terms of the success rate, the detection rate of anatomic abnormality of the biliary system, and the incidence of residual CBD stones.

Results

MRCP preoperatively identified 6 (1.4?%) patients with abnormal biliary systems and 56 with CBD stones, which were endoscopically removed. The success rate of IOC was 93.8?% (399/425). Abnormalities of the biliary system were detected in 12 patients (12/399, 3.0?%) and CBD stones in 8 (8/399, 2.0?%). Of the eight patients with stones, seven had been examined by endoscopy preoperatively and found to have CBD stones. The detection rate of bile duct stones in patients with preoperative endoscopic removal of CBD stones (7/56, 12.5?%) was significantly higher than those with CBD stones first detected during IOC (1/365, 0.3?%) (p?<?0.01). Moreover, no residual CBD stones were detected in patients who were operated on within fewer than 12?days from endoscopic treatment to the operation.

Conclusions

IOC is indicated even after preoperative sphincterotomy for CBD stones. In our study, it resulted in a 12.5?% incidence of persistent stones after sphincterotomy. IOC plays an additional role in detecting CBD stones and in revealing abnormalities of the biliary tree in patients whose biliary tree was preoperatively evaluated by MRCP.     

Treatment of refractory retrobulbar granuloma with rituximab in a patient with ANCA-negative Wegener’s granulomatosis: a case report

Retrobulbar granuloma is one of the serious complications in Wegener’s granulomatosis and often shows resistance to conventional therapy during long-term treatment. The outcome of this complication includes visual loss, orbital and facial deformity, fistula formation, as well as infection. There has been increasing evidence that shows the efficacy of rituximab, a chimeric anti-B cell mAb, for the treatment of autoimmune diseases including Wegener’s granulomatosis. We present a 22-year-old Japanese woman who was diagnosed with Wegener’s granulomatosis complicated by refractory retrobulbar granuloma. She was admitted to our hospital with pain of the right eye and right proptosis during treatment with monthly IVCY for Wegener’s granulomatosis. We diagnosed refractory retrobulbar granuloma by computed tomography (CT) scan and biopsy. She showed a refractory growth of retrobulbar granuloma in spite of negative ANCA. She was also complicated with pulmonary granulomatous lesions in bilateral apices. After approval by an institutional ethical committee and informed consent of this patient, rituximab 375 mg/m² was intravenously administered weekly four times. Concomitant prednisolone 0.5 mg/kg was also administered for 2 weeks and gradually tapered. Treatment of rituximab resulted in prompt relief of symptoms in this case and the reduction of the granuloma. BVAS score also improved from 6 to 0 at 3 months and was kept in remission for 12 months. Circulating CD19-positive cells were kept less than 0.1% during the follow-up. There were no serious adverse events. This case suggests that rituximab is effective for refractory retrobulbar granuloma complicated in Wegener’s granulomatosis even when ANCA titers are negative.     

Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection

HIV-1 infection in the brain induces neuronal apoptosis leading to HIV-associated dementia. To explore the underlying mechanism, we developed a murine model by using human peripheral blood mononuclear cell (PBMC)-transplanted nonobese diabetic (NOD)-severe combined immunodeficiency (SCID) (hu-PBMC-NOD-SCID) mice. Administration of lipopolysaccharide (LPS) to HIV-1-infected hu-PBMC-NOD-SCID mice induced infiltration of HIV-1-infected human cells into the perivascular region of the brain and neuronal apoptosis was found in macrophage (M)-tropic but not T cell (T)-tropic HIV-1-infected brains. The apoptotic neurons were frequently colocalized with the HIV-1-infected macrophages that expressed tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Administration of a neutralizing antibody against human TRAIL but not human TNF-alpha or Fas ligand (FasL) blocked the neuronal apoptosis in the HIV-1-infected brain. These results strongly suggest a critical contribution of TRAIL expressed on HIV-1-infected macrophages to neuronal apoptosis.