Higher intelligence may be a risk factor for postoperative transient disturbance of consciousness after corpus callosotomy.

INTRODUCTION: Corpus callosotomy (CC) is an established surgical option for palliative treatment of medically intractable epilepsy, especially for seizures with drop attacks. We postulated that specific risk factors for post-CC transient disturbance of consciousness (pCTDC) are associated with CC. The purpose of this study was to review patients with intractable epilepsy who underwent CC and to statistically analyze risk factors for pCTDC. METHODS: Inclusion criteria for patients who underwent CC between January 2009 and November 2019 were: (1) ≥2 years old and (2) followed up for more than 8 months. The state of consciousness before and after CC was evaluated with the Glasgow coma scale. We statistically assessed predictors for pCTDC as the primary outcome. RESULTS: Fifty-six patients (19 females, 37 males) were enrolled, and the age range was 2-57 years old. Thirty-seven (66.1%) patients developed pCTDC. The mean period from the beginning of the state of pCTDC to recovery to their baseline conscious level was 4.9 days (range: 2-25 days). All three (100%) normal intelligence level patients, 13 (81%) of 16 patients with a moderately impaired level of intelligence, and 21 (57%) of 37 patients with a severely impaired level of intelligence exhibited pCTDC. Univariate (p = 0.044) and multivariate (p = 0.006) logistic regression analyses for predictors of pCTDC showed that intellectual function was statistically significant. CONCLUSION: Two-thirds of patients developed pCTDC. One risk factor for pCTDC may be higher intellectual function.

Posttraumatic epilepsy may be a state in which underlying epileptogenicity involves focal cortical dysplasia.

INTRODUCTION: The occurrence rate of posttrauma epilepsy ranges widely from 1% to 30%. Little is known about the underlying epileptogenesis of traumatic brain injury (TBI)-related epilepsy (TRE), because no comparison between TRE and TBI without epilepsy has been performed in terms of neuropathology. Therefore, we postulated that different neuropathological factors may be present between TRE and TBI without epilepsy. The purpose of this study was to clarify differences between TRE and TBI without epilepsy. METHODS: We studied patients who experienced severe head trauma and underwent brain surgery. The age range of the patients was 9-71 years old. Patients with medically resistant epilepsy were included in the Epilepsy group, and patients without epilepsy were included in the nonepilepsy group. Pathological findings, age, sex, and cause of head trauma were statistically compared between these two groups. RESULTS: This study involved 10 patients, nine of whom met the inclusion criteria. Pathological findings for all patients in the Epilepsy group included focal cortical dysplasia (FCD) (p = 0.012). CONCLUSION: The difference between TRE and TBI without epilepsy was underlying FCD in patients with TRE.

Seizure focus in the frontal interhemispheric fissure leads to ipsilateral isolated eye deviation.

OBJECTIVE: Few studies have examined the localization of seizures presenting with ictal eye deviation (ED) in the absence of other motor symptoms. We aimed to investigate differences in the localization of the ictal onset zone (IOZ) between patients with isolated ED and those with ED plus head turning (HT) during focal seizures. METHODS: We reviewed intracranial video-EEG data for 931 seizures in 80 patients with focal onset epilepsy in whom the IOZ could be confirmed. The 233 seizures in 49 patients with ED were classified into two semiological groups based on initial ED and the presence/absence of HT: (1) isolated ED (i.e., ED without HT), and (2) ED + HT (i.e., ED with HT). We analyzed the localization and lateralization of IOZs in each semiological group. We performed multivariate logistic regression analysis using a mixed-effects to determine the associations between IOZs and isolated ED/ED + HT. RESULTS: A total of 183 IOZs in 24 patients were included in the isolated ED group, while a total of 143 IOZs in 31 patients were included in the ED + HT group. Sixty-eight IOZs of eight patients in the isolated ED group were located in the ipsilateral frontal interhemispheric fissure (F-IHF). Only ipsilateral F-IHF was significantly associated with isolated ED (odds ratio [OR], 2.43; 95% confidence interval [CI], 0.37-4.49; P = 0.021). The contralateral lateral frontal cortex (latF) (P = 0.007) and ipsilateral mesial temporal region (mT) (P = 0.029) were significantly associated with ED + HT. CONCLUSION: The present study is the first to demonstrate that seizures with an F-IHF focus tend to present with initial ipsilateral isolated ED. This finding may aid in identifying the seizure focus in patients with isolated ED prior to resection.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders.

INTRODUCTION: Little is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. METHODS: A total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. RESULTS: Nineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). CONCLUSION: Epilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

Corpus callosotomy for drug-resistant spasms associated with tuberous sclerosis complex.

BACKGROUND: Corpus callosotomy (CC) has recently been adopted for the treatment of drug-resistant epileptic spasms and tonic spasms. In the present study, we investigated CC outcomes among patients with drug-resistant epileptic spasms or tonic spasms associated with tuberous sclerosis complex (TSC). METHODS: We retrospectively collected data from seven patients (3 women, 4 men) with diagnosed TSC and who were treated using CC at Seirei Hamamatsu General Hospital in Japan. All patients had experienced drug-resistant epileptic spasms (<3 s of muscular contraction) or tonic spasms (>3 s) prior to CC, which were confirmed via video-electroencephalogram monitoring. RESULTS: All patients exhibited multiple bilateral cortical tubers on brain magnetic resonance imaging. The main seizure types were epileptic spasms in four, tonic spasms in one, and both seizure types in two patients. Patients underwent total CC between the ages of 25 months and 21.5 years. Additional resection or disconnection was performed in two patients. The follow-up period after CC ranged between 9 months and 3.5 years. Three patients achieved remission from spasms following CC alone. Two other patients became free from spasms several months after CC but required an additional focus disconnection or medical treatment. The remaining two patients continued to show spasms or asymmetrical tonic seizures. CONCLUSION: Total CC resulted in freedom from drug-resistant epileptic or tonic spasms in several patients with TSC. Stepwise progression from CC to additional resection or disconnection surgery may aid in the treatment of spasms secondary to TSC.

Inclusion of general physicians in the multidisciplinary treatment team for epilepsy may lead to an economic benefit.

INTRODUCTION: The purpose of this study was to compare epileptic seizure control and economic impact in patients with epilepsy between when they were seen by general physicians (GPs) versus epilepsy specialists. METHOD: We began distributing a booklet we named the "Epi Passport" to patients with epilepsy in December 2014 to share information within the regional epilepsy network of GPs, epilepsy specialists, and patients (Gep). We compared seizure control and household income levels before and after the introduction of this booklet. RESULTS: There was no significant difference in seizure control between patients who saw specialists or GPs (P = 0.215). Significant increases in household income were seen among 134 patients (36.6%) in the post-Epi Passport period who were primarily seen by GPs (P < 0.001). However, 35 patients (9.6%) showed a decrease in income between periods, and 197 patients (53.8%) showed no change. Age of 20-39 years old was significantly associated with increases in household income (P = 0.0287). CONCLUSION: After the introduction of the Epi Passport, about one-third of the patients with epilepsy who were mainly seen by GPs in their community showed an increase in household income. There was no difference in seizure control among those who saw a GP or a specialist. Inclusion of GPs in the multidisciplinary treatment team for epilepsy may lead to increased patient income because of the fact that patients can manage their epilepsy in their community using their GP.

Vascular Endothelial Growth Factor in Brain Edema Formation After Subarachnoid Hemorrhage.

Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of brain edema formation after experimental subarachnoid hemorrhage (SAH). In this study, we evaluated the effect of anti-VEGF antibody neutralization on brain edema formation after experimental SAH in mice. Mice underwent sham operation or filament puncture SAH and were assigned to sham, SAH + vehicle, or SAH + anti-VEGF antibody groups. Vehicle or anti-VEGF antibody was administrated by an intracerebroventricular injection at 30 min post-SAH. After 24 h of SAH modeling, neurological score was recorded to evaluate neurobehavioral functions, brain water content was calculated to assess the level of brain edema, and immunohistochemistry of immunoglobulin (Ig) G was performed to evaluate the permeability of the blood-brain barrier (BBB). Anti-VEGF antibody significantly ameliorated neurological score and brain edema after SAH compared with the SAH + vehicle group. Immunohistochemistry showed that post-SAH IgG extravasation in brain tissue was suppressed by anti-VEGF antibody. This study suggests that VEGF is involved in brain edema formation after SAH, and that anti-VEGF antibody can decrease BBB permeability, suppress brain edema formation, and improve functional outcome after 24 h of SAH.

The Role of Matricellular Proteins in Brain Edema after Subarachnoid Hemorrhage.

Accumulated evidence suggests that blood-brain barrier disruption or brain edema is an important pathologic manifestation for poor outcome after aneurysmal subarachnoid hemorrhage. Many molecules may be involved, acting simultaneously or at different stages during blood-brain barrier disruption via multiple independent or interconnected signaling pathways. Matricellular protein is a class of nonstructural, secreted, and multifunctional extracellular matrix proteins, which potentially mediates brain edema formation. This study reviews the role of osteopontin and tenascin-C, representatives of matricellular proteins, in the context of brain edema formation after subarachnoid hemorrhage in both clinical and experimental settings.

The region from phenylalanine-28 to lysine-50 of a yeast mitochondrial ATPase inhibitor (IF1) forms an α-helix in solution.

A mitochondrial ATPase inhibitor, IF1, is a 63 amino acid residue protein that regulates the activity of ATP synthase (F(1)F(o)-ATPase). In the present study, we constructed mutant IF1 proteins with proline residues inserted into a wide range of their primary structures to determine the location and function of α-helix in the protein. A total of 11 yeast IF1 protein mutants were expressed and purified. Proline insertions in the region 28-50 reduced α-helical contents, indicating that the region formed a helix in solution. Oligomer formation of proline mutants at the C-terminal 38-60 region was markedly reduced, indicating that the region is required for oligomerization of the protein. Proline mutants at the N-terminal 18-39 region did not inhibit F(1)F(o)-ATPase, indicating that the region is required for ATPase inhibitory activity. Inhibition of a proline insertion mutant between residues 44 and 45 that lost a large portion of the α-helix was slower, although the maximal inhibition level of the mutant protein was comparable to that of wild-type IF1. The results suggest that the helix of yeast IF1 facilitates binding to F(1) by promoting initial interaction of the proteins.

High-risk plaque for carotid artery stenting evaluated with 3-dimensional T1-weighted gradient echo sequence.

BACKGROUND AND PURPOSE: Preventing cerebral embolisms is a major concern with carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS. METHODS: We performed quantitative analyses of the characteristics of 47 carotid plaques before CAS by measuring the signal intensity ratio (SIR) and plaque volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral emboli. RESULTS: SIR (2.17 [interquartile range 1.50-3.07] versus 1.35 [interquartile range 1.08-1.97]; P=0.010) and plaque volume (456 mm(3) [interquartile range 256-696] versus 301 mm(3) [interquartile range 126-433]; P=0.008) were significantly higher in the group of patients positive for DWI lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In multivariate logistic regression analysis, SIR (P=0.007) and plaque volume (P=0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR (rs=0.42, P=0.005) and plaque volume (rs=0.36, P=0.012) were positively correlated with the number of DWI lesions. From analysis of a receiver-operating characteristic curve, the most reliable cutoff values of SIR and plaque volume to predict DWI lesions related to CAS were 1.80 and 373 mm(3), respectively. CONCLUSIONS: Quantitative evaluation of carotid plaques using 3D T1GRE images may be useful in predicting cerebral embolism related to CAS.

Laminin-1 promotes enteric nervous system development in mouse embryo.

BACKGROUND/AIM: Neuronal development is regulated by extracellular environmental factors including nerve growth factor (NGF) and laminin. We have previously demonstrated that laminin-1 promotes neurite outgrowth of dorsal root ganglion cells by modulating NGF and integrin signaling. However, information about their effects on the enteric nervous system (ENS) is limited. Recently, we succeeded in visualizing enteric neural crest-derived cell (ENCC) migration using SOX10-Venus transgenic mice, in which ENCC are labeled with a green fluorescent protein, Venus. In this study, we examine the effects of NGF and laminin-1 in ENCC migration using SOX10-Venus mice gut. METHODS: Pregnant SOX10-Venus mice were killed on day 12.5 of gestation. The colorectum was dissected from embryos (n = 10) and placed in culture medium including NGF with or without laminin-1 for 12 h. Extension rates of ENCC migration, colorectum and ENCC migration per colorectum were calculated. RESULTS: Venus positive-ENCC extension rate was significantly higher in the laminin group (n = 5) compared to control (n = 5), 22.84 and 13.96 %, respectively (p < 0.05). The extension rate of the colorectum was not significantly different between the two groups. CONCLUSIONS: Our results suggest that laminin promotes ENCC migration in mice. This technique allowed us to visualize the effects of extracellular molecules on ENCC migration and it potentially provides us with an insight into the pathophysiology of developmental disorders of the ENS, such as Hirschsprung's disease.

Surgical strategy for refractory epilepsy secondary to porencephaly: ictal SPECT may obviate the need for intracranial electroencephalography. Patient series.

BACKGROUND: Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors aimed to determine whether noninvasive evaluations are sufficient in these patients. OBSERVATIONS: Eleven patients were included in this study. The porencephalic cyst was in the left middle cerebral artery (MCA) area in 9 patients, the left posterior cerebral artery area in 1 patient, and the bilateral MCA area in 1 patient. Interictal electroencephalography (EEG) revealed multiregional, bilateral, interictal epileptiform discharges in 5 of 11 patients. In 6 of 10 patients whose seizures were recorded, the ictal EEG was nonlateralizing. Nine patients underwent ictal single-photon emission computed tomography (SPECT), which revealed lateralized hyperperfusion in 8 of 9 cases. Fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for identifying the functional deficit zone. No patient had intracranial EEG. The procedure performed was hemispherotomy in 7 patients, posterior quadrant disconnection in 3 patients, and occipital disconnection in 1 patient. A favorable seizure outcome was achieved in 10 of 11 patients without the onset of new neurological deficits. LESSONS: Ictal SPECT was useful for confirming the side of seizure origin when electroclinical findings were inconclusive. Thorough noninvasive evaluations, including FDG-PET and ictal SPECT, enabled curative surgery without intracranial EEG. Seizure and functional outcomes were favorable.

Semiological differences of focal onset bilateral motor (convulsive) seizure between mesial temporal lobe epilepsy and neocortical epilepsy.

OBJECTIVE: We investigated the semiology of focal onset bilateral motor (convulsive) seizure (FBMS) in patients with intractable focal epilepsy who underwent epilepsy surgery to understand its value in localizing the origin of the seizure. METHODS: The study included 20 patients who underwent resective surgery after intracranial video-EEG monitoring (iEEG) with a favorable seizure outcome (Engel class I), and had at least one FBMS during iEEG. The diagnosis was mesial temporal lobe epilepsy (MTLE) for 7 patients and neocortical epilepsy (NE) for 13 patients (lateral temporal lobe, 3; posterior cortex, 6; frontal lobe, 3; perirolandic, 1). Videotaped FBMSs were carefully analyzed. RESULTS: A generalized tonic phase appeared in all 7 patients with MTLE, but was absent in 6 of the 13 patients with NE (P = .044). Tonic cry was more frequently observed in MTLE than in NE (P = .012). Facial tonicity preceding limb tonicity was more frequently seen in patients with MTLE (P = .001). CONCLUSION: Notably, patients with MTLE and those with NE showed semiological differences during bilateralization. FBMS includes not only focal to bilateral tonic-clonic seizure but also focal to bilateral clonic seizure.

Successful Hemispherotomy in a Patient with Encephalopathy with Continuous Spikes and Waves during Sleep Related to Neonatal Thalamic Hemorrhage: A Case Report with Intracranial Electroencephalogram Findings.

Neonatal thalamic hemorrhage is a strong risk factor for developing encephalopathy with continuous spikes and waves during sleep (ECSWS), even when not accompanied by widespread cortical destruction. The efficacy and indication of resective epilepsy surgery in such patients has not yet been reported. A 4-year-old boy was diagnosed with ECSWS based on strong epileptiform activation during sleep and neurocognitive deterioration. He had a history of left thalamic hemorrhage related to a straight sinus thrombosis during the newborn period. He presented with daily absence seizures that were refractory to medical treatment. At age 5, he underwent intracranial electroencephalogram (EEG) recording using depth and subdural strip electrodes placed in the left thalamus and over bilateral cortex, respectively. Interictal and ictal epileptiform discharges were observed in the thalamus, always preceded by discharges in the left or right parietal lobe. Left hemispherotomy successfully normalized the EEG of his unaffected hemisphere and extinguished his seizures. This is the first case report documenting resective epilepsy surgery in a patient with ECSWS due to neonatal thalamic injury without widespread cerebral destruction. Based on intracranial EEG findings, his injured thalamus did not directly generate the EEG abnormalities or absence seizures on its own. Patients with ipsilateral neonatal thalamic injury and even mild lateralized cortical changes may be candidates for resective or disconnective surgery for ECSWS.

Easy anchoring and smaller skin incision procedure for neuronavigation-based frameless stereoelectroencephalography.

Epilepsy surgery uses both depth electrodes (DEs) and subdural electrodes (SE). DEs have mainly been developed and used in Europe. As we are able to use the DEs safely due to the current advanced level of technology, use of DEs has been increasing rapidly over the last decade. Unlike placement of SEs, which simply requires craniotomy, DE placement generally requires stereotactic techniques such as frame-based stereotactic or robotic arm-based methods. However, such methods are not always available at every epilepsy center. We therefore invented guide pipes for accurate DE placement. With this guide pipe and neuronavigation-based (NB) DE placement system, we are able to place DEs accurately. However, the disadvantages of our original procedure were a relatively large skin incision and the difficulty in anchoring DEs. The purpose of this technical note is to introduce a method to perform NB DE placement with a smaller skin incision and simple anchoring procedure. As we could make the skin incision smaller and achieved easier anchoring of DEs using a titanium plate, we hope this procedure will help facilities to perform DE placement with neuronavigation systems.

Efficacy and Safety of Epilepsy Surgery for Older Adult Patients with Refractory Epilepsy.

PURPOSE: The population of elderly patients with epilepsy has been growing rapidly and the chances of referring older patients with refractory epilepsy for surgical options could be increasing. In general, epilepsy surgery at higher ages has been less likely to be performed, because little is known regarding the risks and benefits in elderly patients. We, therefore, investigated surgical outcomes and comorbidities in a population ≥50 years old who underwent epilepsy surgery. METHODS: Patients ≥50 years old who underwent epilepsy surgery were identified from the database of our epilepsy center for the period from 2009 to 2017. Surgical complications and seizure outcome were reviewed, and seizure outcomes were evaluated using the International League Against Epilepsy (ILAE) surgery outcome scale. RESULTS: The mean age of 32 patients at the time of surgery was 56.1±5.1 years. The mean duration of epilepsy was 23.4±18.5 years and mean follow-up was 2.7±2.0 years. As of the most recent visit, 56.3% of patients remained completely seizure-free (ILAE Class I). The surgery-related complication rate was 11.5%, comprising permanent deficits in 3.8% and transient deficits in 7.7%. CONCLUSION: These results suggest that epilepsy surgery may represent a valuable approach in selected adult patients.

Estimation of Risk Factors for Head Slippage Using a Head Clamp System. A Retrospective Study.

BACKGROUND: Although complications have been associated with head clamp systems, few reports have described head slippage. The present study aimed to determine risk factors for head slippage and speculated that the position of head holder pins might be associated. PATIENTS AND METHODS: We reviewed medical records and compared the positions of the pinned heads of patients on fused preoperative and postoperative computerized tomography (CT) images. We measured the distance between corresponding head pins to determine head slippage. Age, sex, body weight, body mass index, surgical position, surgical duration, craniotomy volume, and the relationship between head pins and the nasion-inion (NI) line were statistically compared between patients with and without head slippage. RESULTS: Head slippage in 3 (10%) of 28 patients was significantly associated with the most caudal pin position (p < 0.001) and craniotomy volume (p = 0.036). Receiver operator characteristics curves indicated a cutoff of 4.5 cm from the NI line (sensitivity and specificity, 1.000 and 0.800, respectively). CONCLUSION: Clamped heads can slip during surgical procedures. We found that one head pin should be located within 4.5 cm from the NI line to avoid head slippage.

Removal of a temporal lobe cavernous angioma to control epileptic seizures in a patient with tuberous sclerosis complex.

PURPOSE: A patient with tuberous sclerosis complex (TSC) and a left temporal cavernous angioma (CA) presented with treatment-resistant epilepsy. We evaluated the patient to determine the best treatment option. PATIENT AND METHODS: A 7-year-old boy with TSC exhibited weekly impaired awareness seizures and was diagnosed with TSC based on the modified Gomez's criteria. The presence of cortical tubers had been noted by his physicians. However, left temporal CA had not been diagnosed. He was referred to our facility for further treatment at the age of 33. Presurgical evaluation in our facility revealed the brain tubers and left temporal CA. Based on his seizure semiology, magnetic resonance imaging, scalp electroencephalogram, and long-term video monitoring, we determined his seizures were from the CA and not the TSC network. We then performed intraoperative-electrocorticography (ECoG). RESULTS: Because the ECoG showed epileptiform discharges from the surrounding area of the CA but not from other areas, we removed the CA. He has been seizure-free for more than 10 years. CONCLUSION: The higher likelihood of TSC as well as greater familiarity with this disorder might lead physicians to overlook the possibility of CA.

Hemispherotomy can cause post-operative strabismus.

BACKGROUND: Hemispherotomy, which involves disconnecting hemispherical fibers, is a treatment option for medically intractable epilepsy. As various neurological disorders can cause strabismus, we hypothesized that hemispherotomy can cause post-operative strabismus in patients with medically intractable epilepsy. METHODS: Nineteen patients underwent the Hirschberg test before and after hemispherical disconnection surgery. Among the 19 patients, 16 patients (six females and 10 males; mean age, 12.2 years; range, 0.17-43 years) who underwent hemispherotomy were included in this study. RESULTS: The difference in the angle between the left and right eyes was significantly widened (p = 0.025). Nine (56%) of 16 patients exhibited post-operative chronic strabismus as evaluated with the Hirschberg test. Intermittent strabismus was noticed by family members or caregivers in 10 (63%) of 16 patients. Patients older than 12 years did not show post-operative strabismus as evaluated by the Hirschberg test. CONCLUSION: Hemispherotomy can cause or worsen post-operative strabismus in pediatric patients.

Gallbladder wall abnormality in biliary atresia of mouse Sox17+/- neonates and human infants.

Biliary atresia (BA) is characterized by the inflammation and obstruction of the extrahepatic bile ducts (EHBDs) in newborn infants. SOX17 is a master regulator of fetal EHBD formation. In mouse Sox17+/- BA models, SOX17 reduction causes cell-autonomous epithelial shedding together with the ectopic appearance of SOX9-positive cystic duct-like epithelia in the gallbladder walls, resulting in BA-like symptoms during the perinatal period. However, the similarities with human BA gallbladders are still unclear. In the present study, we conducted phenotypic analysis of Sox17+/- BA neonate mice, in order to compare with the gallbladder wall phenotype of human BA infants. The most characteristic phenotype of the Sox17+/- BA gallbladders is the ectopic appearance of SOX9-positive peribiliary glands (PBGs), so-called pseudopyloric glands (PPGs). Next, we examined SOX17/SOX9 expression profiles of human gallbladders in 13 BA infants. Among them, five BA cases showed a loss or drastic reduction of SOX17-positive signals throughout the whole region of gallbladder epithelia (SOX17-low group). Even in the remaining eight gallbladders (SOX17-high group), the epithelial cells near the decidual sites were frequently reduced in the SOX17-positive signal intensity. Most interestingly, the most characteristic phenotype of human BA gallbladders is the increased density of PBG/PPG-like glands in the gallbladder body, especially near the epithelial decidual site, indicating that PBG/PPG formation is a common phenotype between human BA and mouse Sox17+/- BA gallbladders. These findings provide the first evidence of the potential contribution of SOX17 reduction and PBG/PPG formation to the early pathogenesis of human BA gallbladders.This article has an associated First Person interview with the joint first authors of the paper.