Static Magnetic Field Stimulation Enhances Shunting Inhibition via a SLC26 Family Cl- Channel, Inducing Intrinsic Plasticity.

Magnetic fields are being used for detailed anatomical and functional examination of the human brain. In addition, evidence for their efficacy in treatment of brain dysfunctions is accumulating. Transcranial static magnetic field stimulation (tSMS) is a recently developed technique for noninvasively modifying brain functions. In tSMS, a strong and small magnet when placed over the skull can temporarily suppress brain functions. Its modulatory effects persist beyond the time of stimulation. However, the neurophysiological mechanisms underlying tSMS-induced plasticity remain unclear. Here, using acute motor cortical slice preparation obtained from male C57BL/6N mice, we show that tSMS alters the intrinsic electrical properties of neurons by altering the activity of chloride (Cl-) channels in neurons. Exposure of mouse pyramidal neurons to a static magnetic field (SMF) at a strength similar to human tSMS temporarily decreased their excitability and induced transient neuronal swelling. The effects of SMF were blocked by DIDS and GlyH-101, but not by NPPB, consistent with the pharmacological profile of SLC26A11, a transporter protein with Cl- channel activity. Whole-cell voltage-clamp recordings of the GlyH-101-sensitive Cl- current component showed significant enhancement of the component at both subthreshold and depolarized membrane potentials after SMF application, resulting in shunting inhibition and reduced repetitive action potential (AP) firing at the respective potentials. Thus, this study provides the first neurophysiological evidence for the inhibitory effect of tSMS on neuronal activity and advances our mechanistic understanding of noninvasive human neuromodulation.

Extended period of ventilation before delayed cord clamping augments left-to-right shunting and decreases systemic perfusion at birth in preterm lambs.

Previous studies have suggested that an extended period of ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. However, it is unknown whether this greater rise in PA flow is accompanied by increases in left ventricular (LV) output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale (FO), with decreased systemic arterial perfusion. Using an established preterm lamb birth transition model, this study compared the effect of a short (∼40 s, n = 11), moderate (∼2 min, n = 11) or extended (∼5 min, n = 12) period of initial mechanical lung ventilation before DCC on flow probe-derived perinatal changes in PA flow, LV output, total systemic arterial blood flow, ductal shunting and FO shunting. The LV output was relatively stable during initial ventilation but increased after DCC, with similar responses in all groups. Systemic arterial flow patterns displayed only minor differences during brief and moderate periods of initial ventilation and were similar after DCC. However, an increase in PA flow was augmented with an extended initial ventilation (P < 0.001), owing to an earlier onset of left-to-right ductal and FO shunting (P < 0.001), and was accompanied by a pronounced reduction in total systemic arterial flow (P = 0.005) that persisted for 4 min after DCC (P ≤ 0.039). These findings suggest that, owing to increased left-to-right shunting and a greater reduction in systemic arterial perfusion, an extended period of ventilation before DCC does not result in greater perinatal circulatory benefits than shorter periods of initial ventilation in the birth transition. KEY POINTS: Previous studies suggest that an extended period of initial ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. It is unknown whether this greater rise in PA flow is accompanied by an increased left ventricular output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale, with decreased systemic arterial perfusion. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent a brief (∼40 s), moderate (∼2 min) or extended (∼5 min) period of ventilation before DCC. Perinatal changes in left ventricular output were similar in all groups, but extended initial ventilation augmented both perinatal increases in PA flow, owing to earlier onset and greater left-to-right ductal and foramen ovale shunting, and perinatal reductions in total systemic arterial perfusion. Extended ventilation before DCC does not confer a greater perinatal circulatory benefit than shorter periods of initial ventilation.

Atrial Mechanics, Atrial Cardiomyopathy and Impact of Atrial Interventions.

Our comprehension of atrial mechanics, atrial cardiomyopathy and their clinical implications across various cardiovascular conditions has advanced significantly. Atrial interventions can have differing effects on atrial mechanics. With the rapid increase in the use of atrial interventions, it is crucial for investigators and clinicians to acknowledge the potential adverse effects of these interventions on atrial mechanics that might not be clinically significant at the time of interventions. Recognizing the preclinical stage of atrial maladaptation might enable early interventions before the development of irreversible atrial remodeling and clinical manifestation. We review normal atrial function and mechanics, and atrial cardiomyopathy in select cardiovascular conditions. We also summarize and discuss the current evidence of the impact of various atrial interventions on atrial function and mechanics.

A new spectrum of neonatal urethral pathologies in the era of early vesicoamniotic shunting?

PURPOSE: Intrauterine vesicoamniotic shunting (VAS) was shown to affect survival of male fetuses with megacystis in suspected lower urinary tract obstruction (LUTO). Data on postnatal management are largely lacking. We aim to describe the pathologies diagnosed in children born after vesicoamniotic shunt placement in early pregnancy for megacystis. METHODS: All newborns with previous intrauterine VAS treated in our institution were analyzed retrospectively. We evaluated the clinical spectrum of urethral pathologies. We also compared patients who received a shunt before the 17th gestational week with those who received it later. RESULTS: Between 2014 and 2023, 26 patients (all male) with a history of VAS for suspected LUTO were treated in our institution postnatally. Five fetuses with dislocated shunts underwent re-implantation in utero. Overall, premature birth before the 38th week of gestation was observed in 14 patients. Seven patients received a Harrison® shunt whereas 19 received a Somatex® shunt. Twelve patients required surgical shunt removal under general anesthesia due to shunt migration/embedding. Posterior urethral valves were found in 10/26 patients, 10/26 patients showed a urethral hypoplasia [Fig. 1] and two patients had urethral duplications. In two patients, we identified a prune belly syndrome. One patient had posterior and anterior urethral valves. One patient had a high grade bilateral vesicoureteral reflux without LUTO. The 11 patients shunted early (before 17GW) showed a trend towards a higher proportion of urethral hypoplasia in the early shunt group (54% vs. 26%) without statistical significance. CONCLUSION: In our observation, patients treated with VAS had a noticeable high proportion of complex urethral pathologies such as urethral hypoplasia. These data should be taken into consideration for prenatal counselling of parents and planning of postnatal management.

Widespread haemorrhages in infants post-shunting (WHIPS): clinical features, risk factors and neuroimaging characteristics of a rare and under-recognised phenomenon.

PURPOSE: Infants undergoing CSF shunting procedures face a rare complication which we propose to rename "Widespread Haemorrhages in Infants Post-Shunting" (WHIPS) to better capture this unique phenomenon specific to infants undergoing CSF diversion. Our objective is to analyse the risk factors for WHIPS development and provide a detailed neuroradiological description of these haemorrhages. MATERIALS AND METHODS: A radiology information system (RIS) was searched using the search terms "shunt" and/or "catheter" and/or "drain" and/or "ventriculoperitoneal" and/or "VP" between September 2008 to January 2021 for patients < 12 months of age. Clinical data was compiled for each patient meeting the inclusion criteria. Included cases were reviewed by three radiologists for the presence of WHIPS with calculation of the bifrontal ratio and documenting haemorrhage number, morphology, location and lobar distribution. RESULTS: 51 patients met inclusion criteria, 8 WHIPS patients and 43 controls. There was a statistically significant correlation between a larger post-op head circumference and WHIPS (p = 0.04). WHIPS was associated with post-haemorrhagic hydrocephalus and post-infectious hydrocephalus (p = 0.009). WHIPS were identified in the cortico-subcortical regions, periventricular white matter, and deep white matter. Haemorrhages were either punctate, ovoid or confluent. Haemorrhages ranged from single to innumerable. CONCLUSIONS: WHIPS represent a rare and under-recognised complication of CSF shunting unique to the infantile population. We postulate deep and superficial medullary venous haemorrhage as an underlying mechanism related to disordered intracranial hydrodynamics which are exacerbated in the infantile population due to underdeveloped arachnoid granulations and a compliant skull.

Postoperative disappearance of leptomeningeal enhancement around the brainstem in glioblastoma.

PURPOSE: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. METHODS: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. RESULTS: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. CONCLUSIONS: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.

TEMPI syndrome: A clinical, light-microscopic and phenotypic evaluation with review of the literature.

BACKGROUND AND OBJECTIVES: TEMPI (telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonaryshunting) syndrome is a rare multisystemic disease classified as a monoclonal gammopathy of cutaneous significance. The pathogenesis and etiology of TEMPIare not well known because of the rarity of this disorder. Although telangiectasias are the hallmark of this syndrome, skin biopsies are rarely performed. We aim to further characterize TEMPI syndrome through the evaluationof a skin biopsy. METHODS: We reviewed the histopathology and immunophenotypic profile of a skin biopsy from a 53-year-oldwoman diagnosed with TEMPI syndrome. Other components of her syndromic complex included an IgA myeloma, elevated vascular endothelial growth factor (VEGF), and erythrocytosis. RESULTS: A biopsy showed prominent vascular ectasia with some degree of microvascular basement membranezone thickening. Our patient had a reduction in neoplastic plasma cell burdenand clearing of her telangiectasias following myeloma directed treatment. CONCLUSIONS: TEMPI can beviewed as a reactive vascular paraneoplastic syndrome in the setting of a plasma cell dyscrasia. Elaboration of VEGF from neoplastic plasma cells is likely pathogenetically implicated and appears to be a common link that explains other vascular lesions associated with monoclonal gammopathy syndromes.

Classification of the relationship between suprasellar arachnoid cyst and hydrocephalus based on treatment modalities: shunting versus neuroendoscopic approaches.

PURPOSE: Children diagnosed with suprasellar arachnoid cysts often concurrently have hydrocephalus. This study aims to classify the relationship between suprasellar arachnoid cysts and hydrocephalus, discussing surgical strategies-shunting or neuroendoscopic approaches-and their sequence, based on this classification. METHODS: A retrospective analysis was conducted on 14 patients diagnosed with suprasellar arachnoid cysts and hydrocephalus, treated surgically by the first author between January 2016 and December 2020. Clinical features, radiological findings, surgical strategies, and outcomes were reviewed. The classification of the relationship between the suprasellar arachnoid cysts and hydrocephalus was developed and illustrated with specific cases. Recommendations for future surgical management based on this classification are provided. RESULTS: We classified the relationship between suprasellar arachnoid cysts and hydrocephalus into three categories. SACH-R1, the direct type, represents cases where the cysts cause obstructive hydrocephalus. Here, neuroendoscopic ventriculocystocisternostomy (VCC) effectively treats both conditions. SACH-R2, the juxtaposed type, involves concurrent occurrences of cysts and hydrocephalus without a causative link. This is further subdivided into SACH-R2a, where acute progressive communicating hydrocephalus coexists with the cyst, initially managed with a ventriculoperitoneal shunt, followed by VCC upon stabilization of hydrocephalus; and SACH-R2b, where the cyst coexists with chronic stable communicating hydrocephalus, first addressed with VCC, followed by monitoring and potential secondary shunting if needed. Key factors differentiating SACH-R2a from SACH-R2b include the patient's age, imaging signs of fourth ventricle and cisterna magna enlargement, and the rapid progression or chronic stability and severity of hydrocephalus symptoms. SACH-R3, the reverse type, describes scenarios where shunting for hydrocephalus leads to the development or enlargement of the cyst, managed via neuroendoscopic VCC with precautions to prevent infections in existing shunt systems. CONCLUSION: The simultaneous presence of suprasellar arachnoid cysts and hydrocephalus requires a nuanced understanding of their complex relationship for optimal surgical intervention. The analysis and classification of their relationship are crucial for determining appropriate surgical approaches, including the choice and sequence of shunting and neuroendoscopic techniques. Treatment should be tailored to the specific type identified, rather than blindly opting for neuroendoscopy. Particularly for SACH-R2a cases, we recommend initial ventriculoperitoneal shunting.

Presynaptic coupling by electrical synapses coordinates a rhythmic behavior by synchronizing the activities of a neuron pair.

Electrical synapses are specialized structures that mediate the flow of electrical currents between neurons and have well known roles in synchronizing the activities of neuronal populations, both by mediating the current transfer from more active to less active neurons and by shunting currents from active neurons to their less active neighbors. However, how these positive and negative functions of electrical synapses are coordinated to shape rhythmic synaptic outputs and behavior is not well understood. Here, using a combination of genetics, behavioral analysis, and live calcium imaging in Caenorhabditis elegans, we show that electrical synapses formed by the gap junction protein INX-1/innexin couple the presynaptic terminals of a pair of motor neurons (AVL and DVB) to synchronize their activation in response to a pacemaker signal. Live calcium imaging reveals that inx-1/innexin mutations lead to asynchronous activation of AVL and DVB, due, in part, to loss of AVL-mediated activation of DVB by the pacemaker. In addition, loss of inx-1 leads to the ectopic activation of DVB at inappropriate times during the cycle through the activation of the L-type voltage-gated calcium channel EGL-19. We propose that electrical synapses between AVL and DVB presynaptic terminals function to ensure the precise and robust execution of a specific step in a rhythmic behavior by both synchronizing the activities of presynaptic terminals in response to pacemaker signaling and by inhibiting their activation in between cycles when pacemaker signaling is low.

Transesophageal echocardiography of cardiac function in Nile crocodiles - A novel tool for assessing complex hemodynamic patterns.

BACKGROUND: The crocodilian heart is unique among reptiles with its four-chambered structure and complete intracardiac separation of pulmonary and systemic blood flows and pressures. Crocodiles have retained two aortic arches; one from each ventricle, that communicate via Foramen of Panizza, immediately distally from the aortic valves. Moreover, crocodiles can regulate vascular resistance in the pulmonary portion of the right ventricular outflow tract (RVOT). These unique features allow for a complex regulation of shunting between the pulmonary and systemic circulations. Studies on crocodile shunting have predominantly been based on invasive measurements, but here we report on the use of echocardiography. METHODS: Experiments were performed on seven pentobarbital anaesthetized juvenile Nile crocodiles (length and mass of 192 ± 13 cm and 26 ± 5 kg, respectively). Echocardiographic imaging was performed using a transesophageal (TEE) approach. All images were EKG-gated. RESULTS: We obtain excellent views of cardiac structures and central vasculature through the esophagus. Standard imaging planes were defined for both long- and short axis views of the left ventricle and truncus arteriosus. For the RV, only a short axis view could be obtained. Color Doppler was used to visualize flow. Pulsed waved Doppler for measuring flow profiles across the atrioventricular valves, in the two RVOTs and the left ventricular outflow tract. Shunting across the Foramen of Panizza could be visualized and gated to the EKG. CONCLUSION: TEE can be used to image the unique features of the crocodile heart and allow for in-vivo imaging of the complex shunting hemodynamics, including timing of cardiac shunts.

Curcumol Attenuates Portal Hypertension and Collateral Shunting Via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats.

Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway.

Prospective single-center study on the reliability of ipsilateral cerebral oximetry using near-infrared spectroscopy as a predictor for selective shunting during carotid endarterectomy.

OBJECTIVE: Many techniques are available for the intraoperative assessment of brain perfusion during carotid endarterectomy, such as carotid stump pressure, near-infrared spectroscopy, somatosensory evoked potentials, transcranial Doppler, electroencephalography, and clinical assessment. The decision for selective carotid shunt insertion is dependent on clinical deterioration or the detection of cerebral hypoperfusion after cross-clamping of the internal carotid artery. Monitoring cerebral oximetry using near-infrared spectroscopy is a noninvasive technique for cerebral oxygen saturation measurement, reflecting changes in cerebral blood flow during carotid endarterectomy. The aim of this study was to evaluate the reliability of near-infrared spectroscopy as a predictor of selective shunting during carotid endarterectomy. METHODS: In total, 47 conventional carotid endarterectomy surgeries were performed at our hospital between March 2016 and December 2021. All surgeries were performed under a regional cervical block supplemented with local infiltration anesthesia. All patients were monitored by cerebral oximetry using bilateral near-infrared spectroscopy probes and clinical assessment through communication with the patient (numerical, visual, and verbal) to indicate a selective shunt. Near-infrared spectroscopy values were recorded before and after internal carotid cross-clamping and after declamping. Any decrease in ipsilateral cerebral oximetry-near-infrared spectroscopy values equal to or more than 20% from the pre-clamping baseline reading associated with deterioration in neurological status (hemiparesis, aphasia, or deterioration in level of consciousness) after internal carotid artery cross-clamping was considered an indication for intraluminal carotid shunting. RESULTS: After internal carotid artery cross-clamping, 5 of 47 patients (10.6%) developed a significant drop in cerebral oxygen saturation associated with obvious clinical assessment deterioration in verbal communication and weakness in contralateral arm power. A Pruitt-Inahara carotid shunt was subsequently inserted, and 42 patients remained stable throughout surgery. The average decline in ipsilateral near-infrared spectroscopy values was 23.8% in patients with clinical deterioration. The average decline was 8.6% in patients who remained stable. CONCLUSIONS: Monitoring ipsilateral cerebral oximetry using near-infrared spectroscopy is an easy and reliable method for indicating selective shunting during carotid endarterectomy. A 20% decrease in ipsilateral brain tissue oximetry after internal carotid artery cross-clamping provides a reliable cut-off value for selective intraluminal carotid shunting during carotid endarterectomy.

Single-center outcome analysis of 46 fetuses with megacystis after intrauterine vesico-amniotic shunting with the Somatex®intrauterine shunt.

OBJECTIVES: To assess the spectrum of underlying pathologies, the intrauterine course and postnatal outcome of 46 fetuses with megacystis that underwent intrauterine vesico-amniotic shunting (VAS) with the Somatex® shunt in a single center. METHODS: Retrospective analysis of 46 fetuses with megacystis that underwent VAS either up to 14 + 0 weeks (early VAS), between 14 + 1 and 17 + 0 weeks (intermediate VAS) or after 17 + 0 weeks of gestation (late VAS) in a single tertiary referral center. Intrauterine course, underlying pathology and postnatal outcome were assessed and correlated with the underlying pathology and gestational age at first VAS. RESULTS: 46 fetuses underwent VAS, 41 (89%) were male and 5 (11%) were female. 28 (61%) fetuses had isolated and 18 (39%) had complex megacystis with either aneuploidy (n = 1), anorectal malformations (n = 6), cloacal malformations (n = 3), congenital anomalies overlapping with VACTER association (n = 6) or Megacystis-Microcolon Intestinal-Hypoperistalsis Syndrome (MMIHS) (n = 2). The sonographic 'keyhole sign' significantly predicted isolated megacystis (p < 0.001). 7 pregnancies were terminated, 4 babies died in the neonatal period, 1 baby died at the age of 2.5 months and 34 (74%) infants survived until last follow-up. After exclusion of the terminated pregnancies, intention-to-treat survival rate was 87%. Mean follow-up period was 24 months (range 1-72). The underlying pathology was highly variable and included posterior urethral valve (46%), hypoplastic or atretic urethra (35%), MMIHS or prune belly syndrome (10%) and primary vesico-ureteral reflux (2%). In 7% no pathology could be detected postnatally. No sonographic marker was identified to predict the underlying pathology prenatally. 14 fetuses underwent early, 24 intermediate and 8 late VAS. In the early VAS subgroup, amnion infusion prior to VAS was significantly less often necessary (7%), shunt complications were significantly less common (29%) and immediate kidney replacement therapy postnatally became less often necessary (0%). In contrast, preterm delivery ≤ 32 + 0 weeks was more common (30%) and survival rate was lower (70%) after early VAS compared to intermediate or late VAS. Overall, 90% of liveborn babies had sufficient kidney function without need for kidney replacement therapy until last follow-up, and 95% had sufficient pulmonary function without need for mechanical respiratory support. 18% of babies with complex megacystis suffered from additional health restrictions due to their major concomitant malformations. CONCLUSIONS: Our data suggest that VAS is feasible from the first trimester onward. Early intervention has the potential to preserve neonatal kidney function in the majority of cases and enables neonatal survival in up to 87% of cases. Despite successful fetal intervention, parents should be aware of the potential of mid- or long-term kidney failure and of additional health impairments due to concomitant extra-renal anomalies that cannot be excluded at time of intervention.

National trends in the endovascular and surgical treatment of idiopathic intracranial hypertension.

BACKGROUND: The pattern of surgical treatments for Idiopathic Intracranial Hypertension (IIH) in the United States is not well-studied, specifically the trend of utilizing endovascular venous stenting (EVS) as an emerging technique. METHODS: In this cross-sectional study, we aimed to explore the national trend of utilizing different procedures for the treatment of IIH including EVS, Optic Nerve Sheath Fenestration (ONSF), and CSF Shunting, with a focus on novel endovascular procedures. Moreover, we explored rates of 90-day readmission and length of hospital stay following different procedures, besides the effects of sociodemographic and clinical parameters on procedure choice. RESULTS: 36,437 IIH patients were identified from records between 2010 and 2018. Those in the EVS group were 29 years old on average, and 93.4 % were female. Large academic hospital setting was independently associated with higher EVS utilization, while other factors were not predictive of procedure choice. The proportion of EVS use in IIH hospitalizations increased significantly from 2010 to 2018 (P < 0.001), while there was a relative decline in the frequency of shunting procedures (P = 0.001), with ONSF utilization remaining stable (P = 0.39). The rate of 90-day readmission and length of hospital stay were considerably lower following EVS compared to other procedures (Ps < 0.001). CONCLUSION: This study presents novel population-level data on national trends in the frequency and outcome of EVS for IIH therapy. EVS was associated with shorter length of hospital stays and fewer readmission rates. In addition, a continuous increase in venous stenting compared to other procedures suggests an increasing role for endovascular therapies in IIH.

[Intrascopic predictors of favorable outcomes after ventriculoperitoneal shunting in Hakim-Adams syndrome: a single-center retrospective non-randomized study]. / Intraskopicheskie prediktory udovletvoritel'nogo iskhoda likvoroshuntiruyushchei operatsii pri sindrome Khakima­Adamsa. Rezul'taty odnotsentrovogo retrospektivnogo nerandomizirovannogo issledovaniya.

The main feature of idiopathic normal pressure hydrocephalus is reversible clinical manifestations after timely ventriculoperitoneal shunting. However, the effectiveness of such interventions does not exceed 85%. Invasive diagnostic methods are used to select candidates for surgery. At the same time, literature data indicate neuroimaging symptoms predicting postoperative outcomes without invasive examination. OBJECTIVE: To identify intrascopic predictors of favorable outcomes after ventriculoperitoneal shunting in Hakim-Adams syndrome; to present a model for evaluating MRI data and selecting candidates for surgery. MATERIAL AND METHODS: A single-center retrospective non-randomized study enrolled head MRI data in patients with idiopathic normal-pressure hydrocephalus who underwent ventriculoperitoneal shunting between September 2020 and March 2022. There were 34 patients including 15 ones in the main group (significant improvement after surgery) and 19 ones in the control group. We analyzed quantitative neuroimaging features: ventriculocranial indices, DESH syndrome (DESH score), angle of corpus callosum at the level of anterior and posterior commissures, dimensions of temporal horns of lateral ventricles, the number of lacunar infarcts in basal ganglia and white matter of hemispheres. RESULTS: We identified the most significant predictors of favorable outcomes after ventriculoperitoneal shunting: Evans index, indexed longitudinal size of lateral ventricles, angle of corpus callosum (at the level of anterior and posterior commissures) and DESH score. We created a classification model using discriminant analysis. This model allows us to predict the outcomes after ventriculoperitoneal shunting. CONCLUSION: A comprehensive assessment of intrascopic symptoms allows us to predict the outcomes after ventriculoperitoneal shunting in patients with Hakim-Adams syndrome. In the future, we can avoid invasive diagnostic manipulations in some patients.

Left atrium decompression devices across the spectrum of ejection fraction in heart failure: an updated systematic review and meta-regression analysis.

BACKGROUND: In patients affected by heart failure (HF) with reduced ejection fraction (HFrEF), pharmacological treatments have been proven to alleviate symptoms and improve prognosis, while no treatment other than sodium-glucose co-transporter-2 inhibitors have demonstrated significant effects in HF with preserved ejection fraction (HFpEF). Left atrium decompression devices (LADd) have been recently investigated as a new interventional approach in patients with HFpEF. OBJECTIVES: To assess the efficacy of LADd on soft endpoints in HF patients across the spectrum of ejection fraction. METHODS: PubMed and Web of Science were searched without restrictions from inception to 28 May 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified main outcomes were the change from baseline in 6-min walking distance (6MWD), NYHA class and health-related quality of life (HRQoL). Secondary outcomes were reduction in HF hospitalizations, echocardiographic, and hemodynamic parameters. RESULTS: Eleven studies, with a total of 547 patients, were included. LADd significantly improved 6MWD by 43.95 m (95% CI 29.64-58.26 m), decreased NYHA class by 0.93 (95% CI 1.20-0.67), and improved HRQoL questionnaire by 20.45 points (95% CI 13.77-27.14) with better results for all outcomes in patients with lower EFs. CONCLUSION: The present meta-analysis suggests that LADd are favorable in improving 6MWD, NYHA class, and HRQoL in HF across a wide spectrum of ejection fraction, with better outcomes in patients with lower EFs. TRIAL REGISTRATION: CRD42022336077, URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336077 .

Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by the age of 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) magnetic resonance imaging, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T2 -relaxation-under-spin-tagging were applied in sequence before and after blood transfusion therapy (n = 32) and in a comparator cohort of nontransfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n = 13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared with OEF using paired statistical tests (significance: two-sided p < 0.05). No significant change in sinus signal was observed in nontransfused participants (p = 0.650), but a reduction was observed in transfused participants (p = 0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pretransfusion (p = 0.011), but not posttransfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.

Single-compartment model of a pyramidal neuron, fitted to recordings with current and conductance injection.

For single neuron models, reproducing characteristics of neuronal activity such as the firing rate, amplitude of spikes, and threshold potentials as functions of both synaptic current and conductance is a challenging task. In the present work, we measure these characteristics of regular spiking cortical neurons using the dynamic patch-clamp technique, compare the data with predictions from the standard Hodgkin-Huxley and Izhikevich models, and propose a relatively simple five-dimensional dynamical system model, based on threshold criteria. The model contains a single sodium channel with slow inactivation, fast activation and moderate deactivation, as well as, two fast repolarizing and slow shunting potassium channels. The model quantitatively reproduces characteristics of steady-state activity that are typical for a cortical pyramidal neuron, namely firing rate not exceeding 30 Hz; critical values of the stimulating current and conductance which induce the depolarization block not exceeding 80 mV and 3, respectively (both values are scaled by the resting input conductance); extremum of hyperpolarization close to the midpoint between spikes. The analysis of the model reveals that the spiking regime appears through a saddle-node-on-invariant-circle bifurcation, and the depolarization block is reached through a saddle-node bifurcation of cycles. The model can be used for realistic network simulations, and it can also be implemented within the so-called mean-field, refractory density framework.

Image quality and related outcomes of the ShuntScope for catheter implantation in pediatric hydrocephalus-experience of 65 procedures.

PURPOSE: Ventricular catheter implantation in pediatric hydrocephalus can become a highly challenging task due to abnormal anatomical configuration or the need for trans-aqueductal stent placement. Transluminal endoscopy with the ShuntScope has been invented to increase the rate of successful catheter placements. This study aims to evaluate ShuntScope's image qualities and related surgical outcomes in the pediatric population. METHODS: A retrospective analysis of all pediatric patients undergoing ventricular catheter placement using the ShuntScope from 01/2012 to 01/2022 in the author's department was performed. Demographic, clinical, and radiological data were evaluated. The visualization quality of the intraoperative endoscopy was stratified into the categories of excellent, medium, and poor and compared to the postoperative catheter tip placement. Follow-up evaluation included the surgical revision rate due to proximal catheter occlusion. RESULTS: A total of 65 ShuntScope-assisted surgeries have been performed on 51 children. The mean age was 5.1 years. The most common underlying pathology was a tumor- or cyst-related hydrocephalus in 51%. Achieved image quality was excellent in 41.5%, medium in 43%, and poor in 15.5%. Ideal catheter placement was achieved in 77%. There were no intraoperative complications and no technique-related morbidity associated with the ShuntScope. The revision rate due to proximal occlusion was 4.61% during a mean follow-up period of 39.7 years. No statistical correlation between image grade and accuracy of catheter position was observed (p-value was 0.290). CONCLUSION: The ShuntScope can be considered a valuable addition to standard surgical tools in treating pediatric hydrocephalus. Even suboptimal visualization contributes to high rates of correct catheter placement and, thereby, to a favorable clinical outcome.

Survival and quality of life after CSF diversion in adult patients with leptomeningeal metastasis-associated hydrocephalus: a systematic review and meta-analysis.

OBJECTIVE: Leptomeningeal metastasis (LM) is associated with altered CSF flow dynamics in 50%-70% of patients. Approximately 1%-5% of patients develop symptomatic LM-associated hydrocephalus (LM-H), which adversely impacts quality of life (QOL), functional status, and overall survival (OS). There is equipoise for CSF diversion procedures in LM-H. This systematic review and meta-analysis aimed to assess the effect of CSF diversion on OS and QOL in this context. METHODS: This systematic review was conducted according to the PRISMA guidelines. PubMed/Medline, Embase, Web of Science, and Scopus were searched for articles that evaluated the role of CSF diversion for LM-H due to systemic cancer in adult patients. A meta-analysis was conducted using random effects models, with mean differences and 95% CIs reported. Bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. RESULTS: Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate HRs for median OS, suggesting no significant effect of shunting on OS (pooled HR 0.42, 95% CI 0.09-1.94, p = 0.27). A difference between preoperative and postoperative Karnofsky Performance Status of mean 17.6 points (95% CI 10.44-24.68, p < 0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67%-100% was observed, with high rates of improvement for headaches and nausea and lower rates for cranial nerve palsies. Complication rates across 9 studies ranged from 0% to 21.1%. CONCLUSIONS: Based on the present findings, shunting does not improve OS but does relieve symptoms, suggesting that individuals who exhibit certain symptoms should be considered for CSF diversion. The present findings prompt the generation of a standardized decision-making tool and a critical analysis of the individual patient risk-benefit ratio. Implementation of these will optimize surgical management of LM-H patients.