Traumatic Brain Injury in Patient with Biparietal Thinning.

A 77-year-old man presented with progressive consciousness disturbance, presumably caused by a backward fall. Head computed tomography findings showed a large intracerebral hemorrhage in the left parietal lobe. Radiated fractures with an oval depression of the bilateral parietal bone crossing the midline were noted. Surgical evacuation of the hemorrhage was performed via a left-sided parietal craniotomy, during which fragments from the fracture with eggshell-like thinning were noted. Biparietal thinning is an uncommon condition noted in radiological findings of a symmetrical oval depression of bilateral parietal bones with reduced diploe thickness. Cases of traumatic brain injury in patients with biparietal thinning have rarely been reported. This condition should be recognized as a possible predisposing factor for traumatic brain injury.

A case of primary aldosteronism with excessive secretion of renin that was unmasked by kidney transplantation.

A 42-year-old man showed marked hypokalemia after kidney transplantation. He was diagnosed with hypertension and suffered from acute myocardial infarction at 33 and 38 years of age. At 40 years of age, hemodialysis was introduced. A left adrenal tumor was noted and suspected as a non-functional adrenal adenoma at that time. Therefore, he received a living-donor kidney transplant at 42 years of age. After kidney transplantation, the serum creatinine level dropped. His blood pressure remained high, and the serum potassium level decreased. The PRA and PAC were elevated, and ARR was not elevated. Based on the results of various confirmatory tests and vein sampling, he was diagnosed with excessive secretion of renin from the native kidneys that was complicated by primary aldosteronism (PA), and left nephrectomy and adrenalectomy were performed. The overproduction of aldosterone in the resected adrenal adenoma and over secretion of renin in the kidney with arteriolosclerosis were immunohistologically confirmed. After surgery, the PAC decreased, but the PRA did not decrease. The postoperative serum potassium level improved, and the blood pressure was well controlled with a small dose of medication. This is the first reported case of PA with hyperreninemia after kidney transplantation. It should be noted that PA in dialysis patients and kidney transplant recipients may not fulfill the usual diagnostic criteria of an elevated ARR. In such patients, PA should be suspected based on the absolute value of the PAC and responsiveness to ACTH stimulation, and adrenal and renal vein sampling is required for a definitive diagnosis.

Single-molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance.

Nanog and Oct4 are core transcription factors that form part of a gene regulatory network to regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells (ESCs). To understand their function in the pluripotency maintenance, we visualised and quantified the dynamics of single molecules of Nanog and Oct4 in a mouse ESCs during pluripotency loss. Interestingly, Nanog interacted longer with its target loci upon reduced expression or at the onset of differentiation, suggesting a feedback mechanism to maintain the pluripotent state. The expression level and interaction time of Nanog and Oct4 correlate with their fluctuation and interaction frequency, respectively, which in turn depend on the ESC differentiation status. The DNA viscoelasticity near the Oct4 target locus remained flexible during differentiation, supporting its role either in chromatin opening or a preferred binding to uncondensed chromatin regions. Based on these results, we propose a new negative feedback mechanism for pluripotency maintenance via the DNA condensation state-dependent interplay of Nanog and Oct4.

Thyroid Hormone-Activated Signaling Pathways are Essential for Development of Intestinal Stem Cells.

Intestinal homeostasis is maintained by strict regulation of stem cell function. In mammals, several signaling pathways, including the formation of stem cell niches, are involved in stem cell regulation. However, little is known of the molecular mechanisms involved in postembryonic maturation of the vertebrate intestine, that is, the acquisition of cell renewal systems, including stem cell development and niche formation. Using thyroid hormone (TH) -dependent intestinal remodeling during amphibian metamorphosis as a model to study these mechanisms, we found that several signaling pathways, including the SHH/BMP4, WNT, Notch, and Hippo pathways, are regulated by TH and involved in stem cell regulation. In this review, we highlight findings regarding the role of these signaling pathways and discuss potential future avenues of study.

Stem cell development involves divergent thyroid hormone receptor subtype expression and epigenetic modifications in the amphibian intestine during metamorphosis.

In the amphibian intestine during metamorphosis, most of the larval epithelial cells undergo apoptosis, while a small number of the epithelial cells dedifferentiate into stem cells (SCs). The SCs actively proliferate and then newly generate the adult epithelium analogous to the mammalian counterpart, which is continuously renewed from the SCs throughout adulthood. This larval-to-adult intestinal remodeling can be experimentally induced by thyroid hormone (TH) through interacting with the surrounding connective tissue that develops as the stem cell niche. Thus, the amphibian intestine provides us a valuable opportunity to study how the SCs and their niche are formed during development. To clarify the TH-induced and evolutionally conserved mechanism of SC development at the molecular level, numerous TH response genes have been identified in the Xenopus laevis intestine over the last three decades and extensively analyzed for their expression and function by using wild-type and transgenic Xenopus tadpoles. Interestingly, accumulating evidence indicates that thyroid hormone receptor (TR) epigenetically regulates the expression of TH response genes involved in the remodeling. In this review, we highlight recent progress in the understanding of SC development, focusing on epigenetic gene regulation by TH/TR signaling in the X. laevis intestine. We here propose that two subtypes of TRs, TRα and TRß, play distinct roles in the intestinal SC development via different histone modifications in different cell types.

Traumatic intracranial aneurysm in a distal posterior cerebral artery: A case report and literature review.

Background: Traumatic intracranial aneurysms (TICAs) are rare and known to rupture easily and have a high mortality rate. Case Description: An 87-year-old male patient with no neurological deficits presented to our hospital after head trauma. Computed tomography (CT) revealed a tentorial acute subdural hematoma (ASDH). The patient was managed conservatively and discharged home six days after hospitalization. Two days later, the patient returned with a severe headache. CT showed that the ASDH had enlarged and extended from the tentorium to the convexity. CT angiography and digital subtraction angiography revealed a pseudoaneurysm in a branch of the left posterior inferior temporal artery. The patient was diagnosed with an enlarged ASDH due to a ruptured TICA that arose from the P3 segment. We performed endovascular intervention with parent artery occlusion (PAO) using n-butyl-2-cyanoacrylate (NBCA). The parent artery was accessed through the left posterior communicating artery because left vertebral angiography revealed an aplastic left P1 segment. After navigating the microcatheter near the aneurysm, we injected 33% NBCA into the parent artery. The pseudoaneurysm disappeared after injection. The patient was discharged on hospital day 25 despite persistent delirium. Conclusion: This is the first report of a TICA arising from the P3 segment that was treated with PAO using NBCA. TICAs are rare; however, a TICA must be considered when an enlarged hematoma caused by head injury is detected.

Seronegative Full-house Nephropathy with Crohn's Disease.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Lupus nephritis (LN) is a major risk factor for mortality in SLE, and glomerular "full-house" immunofluorescence staining is a well-known characteristic of LN. However, some cases of non-lupus glomerulonephritis can also present with a "full-house" immunofluorescence pattern. We recently encountered a patient with full-house nephropathy (FHN) during adalimumab administration for Crohn's disease. IgA nephropathy or idiopathic FHN was diagnosed, and treatment with steroids was started, after which there was improvement in proteinuria. The prognosis of FHN has been reported to be poor; therefore, aggressive treatment is required for such patients.

Essential roles of YAP-TEAD complex in adult stem cell development during thyroid hormone-induced intestinal remodeling of Xenopus laevis.

During amphibian metamorphosis which is triggered by thyroid hormone (TH), the small intestine is extensively remodeled from the larval to adult form. In the Xenopus laevis intestine, some of the larval epithelial cells dedifferentiate into adult stem cells, which newly form the adult epithelium similar to the mammalian one. We have previously shown that TH-activated Shh, Wnt and Notch signaling pathways play important roles in adult epithelial development. Here we focus on the Hippo signaling pathway, which is known to interact with these pathways in the mammalian intestine. Our quantitative RT-PCR analysis indicates that the expression of genes involved in this pathway including YAP1, TAZ, TEAD1 and core kinases is differently regulated by TH in the metamorphosing intestine. Additionally, we show by in situ hybridization and immunohistochemistry that the transcriptional co-activator YAP1, a major effector of the Hippo signaling, is expressed in the adult stem cells and connective tissue cells surrounding them and that YAP1 protein is localized in either nucleus or cytoplasm of the stem cells. We further show that YAP1 binds its binding partner TEAD1 (transcription factor) in vivo and that their interaction is inhibited by verteporfin (VP). More importantly, by using VP in organ culture of the tadpole intestine, we experimentally demonstrate that the inhibition of YAP1-TEAD1 interaction decreases both TH-induced stem cells expressing LGR5 and nearby connective tissue cells in number and proliferation, leading to the failure of adult epithelial development. Our results indicate that YAP-TEAD complex is required for stem cell development during intestinal remodeling.

Comparison of comfortable and maximum walking speed in the 10-meter walk test during the cerebrospinal fluid tap test in iNPH patients: A retrospective study.

BACKGROUND: The 10-meter walking test (10 MWT) is widely used during a cerebrospinal fluid tap test (CSFTT) for idiopathic normal-pressure hydrocephalus (iNPH). However, various previous studies and guidelines do not specify whether to adopt a comfortable walking speed or maximum walking speed when implementing the 10 MWT. In this study, we analyzed the values of comfortable and maximum walking speeds during the CSFTT in patients who underwent shunt surgery to determine which walking form is desirable for evaluation. METHODS: The patients were 29 consecutive cases in which a CSFTT was performed, followed by shunting, between October 2012 and April 2019. Data on the 10 MWT comfortable walking speed and maximum walking speed were collected, as were data on the timed up and go (TUG) test and Mini-Mental State Examination (MMSE). We analyzed the rate of change in comfortable walking speed and maximum walking speed before CSFTT and on the first day after CSFTT, and the amount of improvement compared to baseline ability. In addition, diagnostic performance was compared using a receiver operating characteristic (ROC) analysis. RESULTS: Twenty-eight patients who underwent shunt surgery improved their symptoms and were designated as shunt responders. The remaining patient who underwent surgery was considered a non-responder with no improvement in symptoms. The parameters of the shunt responders that changed were muscle strength, the 10 MWT, and the TUG test, and there was no significant change in cognitive function. The rate of change, amount of change, and sensitivity were large at a comfortable walking speed, but ROC analysis showed that the maximum walking speed had a large area under the curve and excellent specificity. The higher the preoperative gait function, the lower the improvement rate of gait function. DISCUSSION: The comfortable walking speed is easy to measure, but its specificity is inferior to the maximum walking speed. However, the maximum walking speed may be affected by the ceiling effect and measurement errors. Despite this, we concluded that the maximum walking speed had a better diagnostic performance. Because the causes of gait disturbance in iNPH include decreased muscle output, postural instability, and gait rhythm disorder, and maximum walking speed is strongly related to each of these factors, this accounts for the changes in maximum walking speed. CONCLUSION: In conclusion, although comfortable walking speed was easy to measure in terms of changes and had high sensitivity, the maximum walking speed had the highest specificity and comprehensive diagnostic performance. It is recommended that maximum walking speed be evaluated when making a definitive diagnosis of iNPH.

Duplicated Middle Cerebral Artery Aneurysms Treated by Coil Embolization; A Report of Two Cases and Literature Review.

BACKGROUND: Duplication of the middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery (ICA). Aneurysms at the origin of a DMCA have been reported; however, most have been treated with clipping surgery. Here, we describe two cases of aneurysms at the origin of a DMCA treated with coil embolization. CASE PRESENTATION: Case 1: A seventy-three year-old man presented with severe headache and was diagnosed with subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) and 3-dimensional (3-D) DSA showed an aneurysm arising from a DMCA. Coil embolization was performed with DMCA patency. The patient had an uneventful postoperative course. CASE 1: A 44-year-old woman presented with a history of clipping for an IC-anterior choroidal artery (AchA) aneurysm 8 years prior. Magnetic resonance imaging (MRI) showed regrowth of the aneurysm. 3-D DSA showed an IC-DMCA aneurysm located laterally and distal to the AchA. The DMCA arose from the bottom of the aneurysm. Coil embolization was performed without DMCA occlusion and showed no postoperative ischemic changes. CONCLUSION: An IC-DMCA aneurysm is rare and may be misdiagnosed as an AchA aneurysm. Clinicians should perform a 3D-DSA evaluation if the aneurysm arises from the lateral wall of the IC to obtain a precise diagnosis and to preserve the DMCA during coil embolization.

Two Patients with Large Aneurysms in Whom Coil Embolization with Overlapping LVIS Stents Was Performed.

Objective: We report two patients with unruptured large aneurysms treated by overlapping stent-assisted coil embolization using low-profile visualized intraluminal support (LVIS) stents. Case Presentation: Case 1: An 80-year-old woman presented with abducens nerve palsy due to an internal carotid artery aneurysm. Case 2: A 75-year-old man presented with a partially thrombosed fusiform aneurysm in the vertebral artery (VA). Both patients were treated by overlapping LVIS stent-assisted coil embolization (overlapping LSACE). Digital subtraction angiography (DSA) a few months after embolization demonstrated complete occlusion of the aneurysm, although immediate angiography revealed dome filling. Conclusion: Overlapping LSACE may be an effective treatment method for aneurysms that are difficult to treat by standard SACE and result in better flow-diverting effects.

Thyroid hormone-induced expression of Foxl1 in subepithelial fibroblasts correlates with adult stem cell development during Xenopus intestinal remodeling.

In the Xenopus laevis intestine during metamorphosis, stem cells appear and generate the adult epithelium analogous to the mammalian one. We have previously shown that connective tissue cells surrounding the epithelium are essential for the stem cell development. To clarify whether such cells correspond to mammalian Foxl1-expressing mesenchymal cells, which have recently been shown to be a critical component of intestinal stem cell niche, we here examined the expression profile of Foxl1 in the X. laevis intestine by using RT-PCR and immunohistochemistry. Foxl1 expression was transiently upregulated only in connective tissue cells during the early period of metamorphic climax and was the highest just beneath the proliferating stem/progenitor cells. In addition, electron microscopic analysis showed that these subepithelial cells are ultrastructurally identified as telocytes like the mammalian Foxl1-expressing cells. Furthermore, we experimentally showed that Foxl1 expression is indirectly upregulated by thyroid hormone (TH) through Shh signaling and that TH organ-autonomously induces the Foxl1-expressing cells concomitantly with appearance of the stem cells in the tadpole intestine in vitro. The present results suggest that intestinal niche cells expressing Foxl1 are evolutionally conserved among terrestrial vertebrates and can be induced by TH/Shh signaling during amphibian metamorphosis for stem cell development.

Long-Term Effects of High-Dose Tolvaptan for Autosomal Dominant Polycystic Kidney Disease Patients.

Tolvaptan, a vasopressin V2 receptor antagonist, was initially approved in Japan for treatment of autosomal dominant polycystic kidney disease (ADPKD). Recently, a retrospective study showed that the effect of tolvaptan on kidney function could be sustained for a long period. However, the long-term efficacy and safety of high-dose tolvaptan (120 mg/day) in individual cases remain unknown. We report here 2 Japanese ADPKD patients (males, 36 and 29 years old) treated with tolvaptan (120 mg/day) for 9 years, during which time determinations of estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were performed. In these 2 patients, eGFR prior to therapy was 57.3 and 76.3 mL/min/1.73 m2, respectively, and 30.2 and 43.5 mL/min/1.73 m2, respectively, after 9 years of tolvaptan treatment, for a relatively constant annual decline of -3.01 and -3.64 mL/min/1.73 m2, respectively. As compared to the predicted (calculated) eGFR without tolvaptan treatment, eGFR actually measured was higher by 15.3 and 12.6 mL/min/1.73 m2, respectively, after the 9-year therapy period. In addition, the rate of TKV increase was gradual, 2.4 and 4.7%, respectively, per year during the initial 3-year period, to 6.5 and 12.5%, respectively, per year in the following 6-year period. During the 9 years of treatment, neither patient showed tolvaptan-related adverse events. Our findings suggest that long-term administration of tolvaptan at a high dose is both safe and effective to preserve kidney function, though a gradual increase in TKV was seen in both of the present cases, particularly during the later phase.

Stem cell development involves divergent thyroid hormone receptor subtype expression and epigenetic modifications in the Xenopus metamorphosing intestine.

In the intestine during metamorphosis of the frog Xenopus laevis, most of the larval epithelial cells are induced to undergo apoptosis by thyroid hormone (TH), and under continued TH action, the remaining epithelial cells dedifferentiate into stem cells (SCs), which then newly generate an adult epithelium analogous to the mammalian intestinal epithelium. Previously, we have shown that the precursors of the SCs that exist in the larval epithelium as differentiated absorptive cells specifically express receptor tyrosine kinase-like orphan receptor 2 (Ror2). By using Ror2 as a marker, we have immunohistochemically shown here that these SC precursors, but not the larval epithelial cells destined to die by apoptosis, express TH receptor α (TRα). Upon initiation of TH-dependent remodeling, TRα expression remains restricted to the SCs as well as proliferating adult epithelial primordia derived from them. As intestinal folds form, TRα expression becomes localized in the trough of the folds where the SCs reside. In contrast, TRß expression is transiently up-regulated in the entire intestine concomitantly with the increase of endogenous TH levels and is most highly expressed in the developing adult epithelial primordia. Moreover, we have shown here that global histone H4 acetylation is enhanced in the SC precursors and adult primordia including the SCs, while tri-methylation of histone H3 lysine 27 is lacking in those cells during metamorphosis. Our results strongly suggest distinct roles of TRα and TRß in the intestinal larval-to-adult remodeling, involving distinctive epigenetic modifications in the SC lineage.

Delayed Intracranial Parenchymal Changes After Aneurysmal Coil Embolization Procedures for Unruptured Intracranial Aneurysms.

BACKGROUND: With the recent advances in endovascular treatment devices, it has become standard in wide-neck or large intracranial aneurysms to perform coil embolization with adjunctive techniques. However, device-related perioperative complications have been reported because of the use of more complex systems. OBJECTIVE: To investigate patients who developed multiple parenchymal lesions after undergoing coil embolization for treating an unruptured intracranial aneurysm. METHODS: This study investigated 305 consecutive patients who underwent coil embolization of unruptured intracranial aneurysms between 2015 and 2017. Delayed inflammatory changes referred to the delayed observation of multiple cerebral white matter lesions on follow-up magnetic resonance imaging at an area corresponding to the perfused area of the treatment target vessel. The timing and pattern of onset, device used, the combined use of adjunctive techniques, and the clinical course after steroid treatment were retrospectively investigated. RESULTS: The 7 patients (2.3%) who showed delayed inflammatory changes were all women with a mean age of 59 yr. A mean duration from treatment to onset was 28 d. Symptoms were convulsions in 3 patients, hemiplegia in 2 patients, and homonymous hemianopia in 1 patient. All 7 patients were treated with adjunctive technique including stents, double catheter method, and balloon assist. Response to steroid treatment was satisfactory both clinically and on imaging in all 7 patients. Skin patch test was positive for nickel allergy in 2 patients. CONCLUSION: Clinicians must be fully aware of symptomatic delayed inflammatory changes may occur after endovascular aneurysmal treatment with the use of various devices.

Adenosine Attenuates Aortic Smooth Muscle Cell Calcification through A3 Adenosine Receptor.

Vascular calcification is a typical feature of atherosclerosis and is associated with adverse cardiovascular events such as myocardial infarction and stroke. Several studies have suggested that adenosine, an ATP metabolite may function as an endogenous regulator of arterial calcification. However, its effects on vascular smooth muscle cell calcification have not been clarified. In this study, we investigated the inhibitory effects of adenosine on vascular calcification in vitro by utilizing the culture of human aortic smooth muscle cells (HASMCs). Osteoblastic differentiation of HASMCs was induced by the treatment with oncostatin M and osteogenic differentiation medium. Adenosine and its metabolically stable analogue, 2-chloroadenosine (CADO) significantly reduced matrix mineralization and alkaline phosphatase (ALP) activities in HASMCs. The mRNA expression of tissue non-specific alkaline phosphatase (TNAP) was down-regulated by adenosine and CADO, but the mRNA expression of other osteoblastic differentiation markers, such as Runt-related transcription factor 2 (RUNX2) and bone sialoprotein (BSP)-II, was not significantly affected by these two reagents. Among the adenosine receptor (AR) subtype-selective agonists used, only IB-MECA (A3 AR-selective agonist) significantly decreased in vitro mineralization and ALP activities in HASMCs, but not with CCPA (A1 AR-selective agonist), CGS21680 (A2a AR-selective agonist), or BAY60-6583 (A2b AR-selective agonist). Importantly, IB-MECA also down-regulated expression of TNAP mRNA. Finally, knockdown of A3 AR, but not A1 AR, A2a AR, or A2b AR, significantly reversed the inhibitory actions of adenosine, CADO, or IB-MECA on in vitro calcification and ALP activities in HASMCs. These data suggest that adenosine attenuates HASMC calcification through A3 AR.

Characteristics of cognitive function evaluation using the Montreal cognitive assessment in a cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVES: Though the Japanese version of the Montreal Cognitive Assessment (MoCA-J) scores change after a cerebrospinal fluid tap test (CSFTT), their characteristics remain unclear. To compare patient response rate to changes in cognitive function observed in the cerebrospinal fluid tap test, and to determine which group of patients were good responders. PATIENTS AND METHODS: This study included 32 patients who were suspected of having idiopathic normal pressure hydrocephalus (iNPH) between May 2017 and October 2018. Cases were divided into, following a CSFTT, a gait responder group and a non-responder group. Scores of the MoCA-J were compared and examined before, one day after, and one week after the CSFTT. RESULTS: Significant changes in MoCA-J scores were observed 1 day and 1 week after the CSFTT in the gait responder group. The change in scores was larger, and had a larger effect size, one week after the CSFTT. On assessment, MoCA-J sub-items began to show changes in attention and abstract items one day after the CSFTT, and significant changes were noted in attention and abstract items in addition to executive functions and orientation one week after the CSFTT. The degree of cognitive function before the CSFTT was less closely related to the amount of change. Changes in cognitive function can be assessed at each time point after the CSFTT, and changes in cognitive function are measured regardless of the level of cognitive function. CONCLUSION: These results suggest that evaluating patients with the MoCA-J may potentially support a more accurate iNPH diagnosis.

Oncostatin M induces C2C12 myotube atrophy by modulating muscle differentiation and degradation.

Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays a role in various disorders such as cancer and inflammatory diseases, which are often accompanied by skeletal muscle atrophy, or sarcopenia. However, the role of OSM in the regulation of skeletal muscle mass remains to be identified. In this study, we investigated the effect of OSM on C2C12 myotube formation in vitro. C2C12 myoblasts were induced to differentiate into myotubes for 3 days and then treated with OSM for 24 or 48 h. The diameter of differentiated C2C12 myotubes were reduced by 18.7% and 23.3% compared to control cells after treatment with OSM for 24 and 48 h, respectively. The expression levels of MyoD and myogenin were decreased, while those of atrogin-1, CCAAT/enhancer binding protein δ, and OSM receptor were increased in C2C12 myotubes treated with OSM for 24 h compared to control cells. Furthermore, the inhibitory effect of OSM on myotube formation was significantly attenuated by pretreatment with an inhibitor of signal transducer and activator of transcription (STAT) 3 or by knockdown of Stat3. Finally, the OSM-induced changes in the expression levels of MyoD, myogenin, and atrogin-1 were reversed by pretreatment with an inhibitor of STAT3 or by Stat3 knockdown in C2C12 myotubes. In conclusion, OSM induces C2C12 myotube atrophy by inhibiting myogenic differentiation and activating muscle degradation in a STAT3-dependent manner.

Functional connectivity analysis and prediction of cognitive change after carotid artery stenting.

OBJECTIVE: The neurocognitive course of patients who have undergone cerebral revascularization has been the subject of many studies, and the reported effects of carotid artery stenting (CAS) on cognitive function have varied from study to study. The authors hypothesized that cognitive amelioration after CAS is associated with alteration of the default mode network (DMN) connectivity, and they investigated the correlation between functional connectivity (FC) of the DMN and post-CAS changes in cognitive function in order to find a clinical marker that can be used to predict the effect of cerebral revascularization on patients' cognitive function in this preliminary exploratory study. METHODS: The authors examined post-CAS changes in cognitive function in relation to FC in patients treated for unilateral carotid artery stenosis. Resting-state functional MRI (rs-fMRI) was performed with a 3-T scanner before and 6 months after CAS in 8 patients. Neuropsychological tests (Wechsler Adult Intelligence Scale III and Wechsler Memory Scale-Revised) were administered to each patient before and 6 months after CAS. The DMN was mapped for each patient through independent component analysis of the rs-fMR images, and the correlation between FC of the DMN and post-CAS change in cognitive function was analyzed on a voxel level. Multivariable regression analysis was performed to identify preoperative factors associated with a post-CAS change in cognitive function. RESULTS: Post-CAS cognitive function varied between patients and between categories of neuropsychological tests. Although there was no significant overall improvement in Working Memory scores after CAS, post-CAS Working Memory scores changed in negative correlation with changes in FC between the DMN and the precentral/superior frontal gyrus and between the DMN and the middle frontal gyrus. In addition, the preoperative FC between those areas correlated positively with the post-CAS improvement in working memory. CONCLUSIONS: FC between the DMN and working memory-related areas is closely associated with improvement in working memory after CAS. Preoperative analysis of FC of the DMN may be useful for predicting postoperative improvement in the working memory of patients being treated for unilateral stenosis of the extracranial internal carotid artery.Clinical trial registration no.: UMIN000020045 (www.umin.ac.jp/ctr/index.htm).