Tacrolimus (TAC) is an immunosuppressant drug discovered in 1984 by Fujisawa Pharmaceutical Co., Ltd. This drug belongs to the group of calcineurin inhibitors, which has been proven highly effective in preventing acute rejection after transplantation of solid organs. However, neurotoxicity and nephrotoxicity are its major adverse effects. Posterior reversible encephalopathy syndrome (PRES) is the most severe and dramatic consequence of calcineurin inhibitor neurotoxicity. It was initially described by Hinchey et al. in 1996 [N Engl J Med 1996;334:494–450]. Patients typically present with altered mental status, headache, focal neurological deficits, visual disturbances, and seizures. Magnetic resonance imaging is the most sensitive imaging test to detect this. With the more deep-going studies done recently, we have learnt more about this entity. It was noted that this syndrome is frequently reversible, rarely limited to the posterior regions of the brain, and often located in gray matter and cortex as well as in white matter. Therefore, in this review, the focus is on the current understanding of clinical recognition, pathogenesis, neuroimaging and management of TAC-associated PRES after solid organ transplantation.

Background. Tacrolimus-associated encephalopathy (TAC-E) is usually described under the term of posterior reversible encephalopathy syndrome (PRES). However, a large amount of data has suggested that TAC-E is not a homogenous entity: indeed, TAC-E which is often presented with atypical and potentially misleading imaging characteristics does not always correspond to PRES. Objective. We aimed to identify the spectrum of brain MR imaging of TAC-E and discuss the underlying pathophysiological features. Methods. From September 2008 to October 2010, the neurological statuses of 45 patients, who underwent lung transplantation with TAC as posttransplantation immunosuppressive therapy, were regularly assessed in a prospective study. MRI was repeatedly performed, until recovery, in patients who developed central neurological symptoms. Results. Symptoms suggestive of encephalopathy occurred in five out of 45 patients (11.1%). According to our MRI study, two patients presented with reversible bilateral and relatively symmetric subcortical white matter edema with proximal vasospasms on MRA; however, three other patients were characterized by coexistence of two different lesions including laminar cortical infarcts with hemorrhagic transformation not typically found in PRES and reversible deep white matter edema, associated with distal vasospasms on MRA. Conclusions. It is considered that the mechanism of TAC-E would be more heterogenous than commonly perceived.

Introduction: Increased life expectancy results in a rapid increase of nonagenarian patients presenting with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We conducted this study to assess the efficacy and safety of endovascular thrombectomy (ET) in this age group with use of imaging-based selection. Methods: We retrospectively analyzed clinical and imaging data from 2 different comprehensive stroke centers and compared the outcomes of ET versus intravenous thrombolysis (IVT) alone among eligible nonagenarians with LVO in anterior circulation and evidence of salvageable tissue on brain magnetic resonance imaging (MRI). Results: A total of 617 patients of AIS had been treated with IVT or ET, including 23 eligible nonagenarians. Among these, 9 patients were treated with IVT alone (IVT group) and 14 patients received ET group. Notably, the symptomatic intracranial hemorrhage rates were significantly lower after ET than after IVT (European-Australasian Acute Stroke Study II criteria, 0 vs. 33.3%; p = 0.047; National Institute of Neurological Disorders and Stroke criteria, 7.1 vs. 66.7%; p = 0.005). Moreover, although there were no statistically significant differences between the 2 groups on efficacy, ET tended to lead to greater early neurologic recovery at discharge (71.4 vs. 33.3%, p = 0.102) and improve functional outcome at 90 days (71.4 vs. 44.4%, p = 0.383), respectively. Conclusion: By using MRI-based selection, ET in nonagenarians with AIS caused by LVO within anterior circulation was safe and may lead to improve early neurologic recovery and functional independence at 90 days, as compared with IVT alone. Randomized trial in larger sample size testing efficacy of ET using diffusion-weighted imaging-fluid attenuated inversion recovery mismatch selection in this age group appears feasible.

Background: In the event of middle cerebral artery occlusion (MCAO), leptomeningeal collaterals (LMCs) play a crucial role in determining the survival of brain tissue distal to occlusion. Previous findings indicated that genes controlling arteriogenesis can impact the extent of LMCs. Therefore, probe for potential genetic parameters correlating of arteriogenesis may be clinically useful in predicting LMCs status in MCAO.During the screening process, we focused on repulsive guidance molecule a (RGMa), which has been reported to play a negative role in angiogenesis after stroke by decreasing the proliferation, migration, and tube formation of endothelial cells (ECs) in vivo and in vitro. Indeed, endothelial function plays a main role in arteriogenesis and is essential in determining the LMCs status. Therefore, in present study, we aimed to testify the hypothesis that RGMa might be associated with LMCs status in MCAO. Methods:We prospectively enrolled patients with acute M1 MCA +/− intracranial internal carotid artery (ICA) occlusions (n=96) and healthy controls (n=33). Status of LMCs was evaluated according to computed tomographic angiography (CTA) on admission. Baseline RGMa mRNA expression was quantified by using quantitative real-time PCR.Results: Patients with poor LMCs showed significantly higher RGMa mRNA levels than patients with good LMCs status (P=0.001) as well as healthy controls (P=0.002), respectively; whereas good LMCs group showed similar baseline RGMa levels than controls (P=1.000). RGMa mRNA level and baseline NIHSS score were independent predictors for impaired LMCs. Conclusions:In MCAO patients, elevated PBMCs RGMa mRNA levels were associated with impaired LMCs status, indicating that measurement of RGMa mRNA expression in the early phase of stroke, together with other clinical approaches, was logically expected to be useful for predicting LMCs status. Moreover, a role for RGMa in leptomeningeal arteriogenesis following ischemic stroke can be hypothesized.

Methyl CpG binding protein-2 (MeCP2) is a multifunctional nuclear protein, and regulates dendritic morphology, synaptic transmission, spontaneous neurotransmission, and short-term synaptic plasticity in the central nervous system. This study was designed to investigate the expression of MeCP2 mRNA and protein in intractable temporal lobe epilepsy (TLE) patients and an experimental animal model. MeCP2 expression was detected in 35 temporal neocortex tissue samples from patients with intractable TLE and 14 histologically normal temporal lobe tissue samples from trauma patients without epilepsy by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and double-label immunofluorescence. In addition, the timing of MeCP2 expression was evaluated in the hippocampus and adjacent cortex of lithium chloride/pilocarpine-induced TLE rats and uninduced controls. MeCP2 was found to be expressed mainly in the nuclei of neurons, and not expressed in astrocytes. MeCP2 expression was significantly higher in the TLE patients and rats than in the control groups. Following seizures in the rat model, MeCP2 expression gradually increased in the hippocampus and adjacent cortex during the acute period (days 1 and 2) and the latent period (days 7 and 14), but decreased during the chronic period (days 30 and 60). Up-regulated expression of MeCP2 in intractable TLE patients and experimental animals suggested that MeCP2 may be involved in the pathogenesis of TLE.