Tomohiro Matsuda, Mami Hanaoka, Takeshi Miyamoto, Noriya Enomoto, Hitoshi Niki, Kazuhito Matsuzaki, Koichi Satoh and Yasushi Takagi : Low-profile visualized intraluminal support junior-within-enterprise 2 stent technique for a distal middle cerebral artery fusiform aneurysm: A case report., Surgical Neurology International, 16, 2025.
(Summary)
Aneurysms distal to the M2 segment account for 2-7% of middle cerebral artery (MCA) aneurysms. These aneurysms, which are often small and fusiform, have thin walls and are prone to bleeding. Therefore, neck clipping and aneurysmal coil embolization are difficult to perform. Herein, we report a case of distal MCA fusiform thrombosed large aneurysm in which the patient underwent overlapping stent with coil embolization.A 28-year-old man presented to our hospital due to sudden headache onset. Computed tomography revealed a subarachnoid hemorrhage and oval lesion with calcification in the left sylvian fissure. Digital subtraction angiography revealed an 8-mm fusiform aneurysm in the M2 and M3 segments of the left MCA. We performed palliative coil embolization of the saccular portion of the aneurysm. The patient was discharged 22 days after presentation. Imaging performed 2 months after the initial treatment revealed aneurysm enlargement. Because the patient refused to undergo craniotomy, we performed coil embolization with an overlapping stent. An Enterprise 2 stent was deployed to sufficiently cover the aneurysmal segment. Subsequently, an low-profile visualized intraluminal support junior (LVIS Jr.) stent was placed inside the Enterprise 2 stent, and additional coil embolization was performed. Follow-up imaging 5 months after the second treatment revealed complete resolution of the aneurysm.The LVIS Jr.-within-Enterprise 2 stent technique may resolve fusiform aneurysms located in distal arteries and maintain parent artery patency.
Relin Vliet van, M.P. Meenen David van, Chiara Robba, Raphaël Cinotti, Karim Asehnoune, D. Robert Stevens, Denise Battaglini, Shaurya Taran, Mathieu der Jagt van, Silvio Fabio Taccone, Frederique Paulus, J. Marcus Schultz, sélim Paër Abback, Anaïs Codorniu, Giuseppe Citerio, Ludovica Vittoria Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Giuseppina Jessica Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Chiara Robba, Denise Battaglini, Patrick Biston, Fathi Mohamed Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter Vliet van, Marcel Benjamin Gerretsen, Xochitl Iris Ortiz-macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, J. Wytze Vermeijden, Daniel Alexander Cornet, Reyes Sergio Inurrigarro, Lara Rafael Cirino Domínguez, Mercedes Maria Bellini, Milagros Maria Gomez-Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Carlos Roberto Miranda-Ackerman, José Francisco Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Basheer Hana Yahya, Ala Khaled, Mohamed Ghula, Cracchiolo Andrea Neville, Daniela Maria Palma, Cristian Deana, Luigi Vetrugno, J. Chavez Manuel Rivera, Mendoza Rocio Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu der Jagt van, Job Steenkiste van, Hazem Ahmed, Edward Alexander Coombs, Jessie Welbourne, Velarde Ana Alicia Pineda, Nubert Víctor Hugo Castillo, A. Mohammed Azab, Y. Ahmed Azzam, M.P. Meenen David van, Adrian Gilberto Gascav, Alfredo Arellano, Forttino Galicia-Espinosa, Carlos José García-Ramos, Ghanshyam Yadav, Kumar Amarendra Jha, Vincent Robert-Edan, Andre Pierre Rodie-Talbere, et al. and Yoshitoyo Ueno : Association of age with extubation failure in neurocritical intensive care unit patients--Insight from an international prospective study named ENIO, Journal of Critical Care, 88, 155067, 2025.
(Summary)
To assess the association of age with extubation failure in neurocritical care patients. Posthoc analysis of the 'Extubation strategies in Neuro-Intensive care unit patients and associations with Outcomes (ENIO) study', an international prospective observational study. ENIO was conducted in 73 centers in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Scale score 12 and receiving ventilationfor at least 24 h were included. We categorized patients into four age groups based on age quartiles. This analysis included 1095 patients with a median age of 53 [35 to 65] years. Younger patients were more likely to be admitted with traumatic brain injury, whereas older patients more often had cerebral hemorrhage, ischemic stroke, central nervous infection, or brain malignancies. Extubation failure occurred in 209 (19 %) patients. In the unadjusted analysis, older patients had a higher risk of extubation failure (odds ratio (OR), 1.012 [95 %-confidence interval (CI) 1.004 to 1.021]; P = 0.006). However, after adjusting for confounding factors, the effect of age on extubation failure was no longer significant (OR, 1.008 [0.997 to 1.019]; P = 0.172). In this international cohort of intubated and ventilated neurocritical care patients, after adjusting for baseline covariates and for previously identified risk factors for extubation failure, age was not associated with extubation failure. Age may not be a factor to consider in extubation decisions for brain-injured patients. ENIO is registered at clinicaltrials.gov (study identifier NCT03400904).
(Keyword)
Age groups / Airway extubation / Brain injury / Critical care / Mechanical / Ventilators
Tomohiro Matsuda, Mami Hanaoka, Noriya Enomoto, Tadashi Yamaguchi, Takeshi Miyamoto, Hitoshi Niki and Kazuhito Matsuzaki : Combined Mechanical Thrombectomy for Multiple Cerebral Venous Sinus Thrombosis Involving the Straight Sinus: A Case Report., NMC Case Report Journal, 11, 227-231, 2024.
(Summary)
The proportion of cerebral venous sinus thrombosis involving the straight sinus (StS) is low, and the prognosis is poor. We report a case of multiple sinus thrombosis involving StS in which the patient underwent mechanical thrombectomy (MT) using a stent retriever and an aspiration catheter (combined MT) with a good postoperative course. A 15-year-old girl was admitted to our hospital with rapid loss of consciousness. Magnetic resonance imaging (MRI) revealed thrombosis of the bilateral internal cerebral veins, vein of Galen, StS, torcular herophili (TH), and right transverse sinus (TS), as well as edema mainly in the left thalamus, basal ganglia, and corpus callosum. Systemic heparinization was initiated, and combined MT was performed. Although complete recanalization of the TH and right TS via the left internal jugular vein was achieved, the microwire could not be advanced to the StS. Hence, the approach route was changed to remove the thrombus from the superior sagittal sinus and successfully reach the StS via the right TS. Partial recanalization of the StS was achieved, and venous congestion was improved. Two months after MT, the patient returned to school without neurological deficits. MRI performed 3 months after MT revealed disappearance of the edema and complete recanalization of the StS. In this case, StS catheterization via the left TS was not possible. However, we could reach the right TS, which were recanalized first. Partial recanalization of the StS can be expected a good prognosis under the patency of the TH and TS.
Noriya Enomoto, Kazuhito Matsuzaki, Tomohiro Matsuda, Tadashi Yamaguchi, Takeshi Miyamoto, Mami Hanaoka, Natsumi Teshima, Ayato Kageyama, Yuichi Satoh, Tatsuya Haboshi, Masaaki Korai, Kenji Shimada, Hitoshi Niki, Koichi Satoh and Yasushi Takagi : Effectiveness of hinge craniotomy as an alternative to decompressive craniectomy for acute subdural hematoma, Acta Neurochirurgica, 166, 1, 272, 2024.
(Summary)
Acute subdural hematoma (ASDH) is a life-threatening condition, and hematoma removal is necessary as a lifesaving procedure when the intracranial pressure is highly elevated. However, whether decompressive craniectomy (DC) or conventional craniotomy (CC) is adequate remains unclear. Hinge craniotomy (HC) is a technique that provides expansion potential for decompression while retaining the bone flap. At our institution, HC is the first-line operation instead of DC for traumatic ASDH, and we present the surgical outcomes. From January 1, 2017, to December 31, 2022, 372 patients with traumatic ASDH were admitted to our institution, among whom 48 underwent hematoma evacuation during the acute phase. HC was performed in cases where brain swelling was observed intraoperatively. If brain swelling was not observed, CC was selected. DC was performed only when the brain was too swollen to allow replacement of the bone flap. We conducted a retrospective analysis of patient demographics, prognosis, and subsequent cranial procedures for each technique. Of the 48 patients, 2 underwent DC, 23 underwent HC, and 23 underwent CC. The overall mortality rate was 20.8% (10/48) at discharge and 30.0% (12/40) at 6 months. The in-hospital mortality rates for DC, HC, and CC were 100% (2/2), 21.7% (5/23), and 13.0% (3/23), respectively. Primary brain injury was the cause of death in five patients whose brainstem function was lost immediately after surgery. No fatalities were attributed to the progression of postoperative brain herniation. In only one case, the cerebral contusion worsened after the initial surgery, leading to brain herniation and necessitating secondary DC. The strategy of performing HC as the first-line operation for ASDH did not increase the mortality rate compared with past surgical reports and required secondary DC in only one case.
(Keyword)
Acute subdural hematoma / Decompressive craniectomy / Head trauma / Hinge craniotomy
Shaurya Taran, Bastien Perrot, Federico Angriman, Raphael Cinotti, Sélim Paër Abback, Anaïs Codorniu, Giuseppe Citerio, Vittoria Sala Ludovica, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Jessica Maugeri Giuseppina, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Chiara Robba, Denise Battaglini, Patrick Biston, Mohamed Al-Gharyani Fathi, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter Vliet Van, Benjamin Gerretsen Marcel, Iris Ortiz-Macias Xochitl, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, J. Wytze Vermeijden, Alexander Cornet Daniel, Sergio Inurrigarro Reyes, Rafael Lara Domínguez Cirino, Maria Bellini Mercedes, Maria Gomez Haedo Milagros, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Roberto Miranda-Ackerman Carlos, Francisco Barbosa-Camacho José, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Hana Yahya Basheer, Ala Khaled, Mohamed Ghula, Cracchiolo Andrea Neville, Palma Daniela Maria, Cristian Deana, Luigi Vetrugno, J. Chavez Manuel Rivera, Rocio Trujillo Mendoza, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu Der Jagt Van, Job Steenkiste Van, Hazem Ahmed, Alexander Coombs Edward, Jessie Welbourne, Alicia Pineda Ana Velarde, Hugo Castillo Víctor Nubert, A. Mohammed Azab, Y. Ahmed Azzam, Michael Van Meenen David Paul, Gilberto Gasca Adrian, Alfredo Arellano, Forttino Galicia-Espinosa, José García-Ramos Carlos, Ghanshyam Yadav, Amarendra Jha Kumar, Vincent Robert-Edan, Andre Pierre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Gilberto Gasca Adrian, Alfredo Arellano, Syed Reza Tariq, Mozaffer Md Hossain, et al. and Yoshitoyo Ueno : Evaluating the Sum of Eye and Motor Components of the Glasgow Coma Score As a Predictor of Extubation Failure in Patients with Acute Brain Injury, Critical Care Medicine, 52, 8, 1258-1263, 2024.
(Summary)
To evaluate the association between the pre-extubation sum of eye and motor components of the Glasgow Coma Score (GCS-EM) and odds of extubation failure in patients with acute brain injury being liberated from mechanical ventilation. Secondary analysis of a prospective, multicenter observational study ( ClinicalTrials.gov identifier NCT03400904). Sixty-three hospital sites worldwide, with patient recruitment from January 2018 to November 2020. One thousand one hundred fifty-two critically ill patients with acute brain injury, with a median age of 54 years, of whom 783 (68.0%) were male, 559 (48.5%) had traumatic brain injury, and 905 (78.6%) had a GCS-EM greater than 8 before extubation (scores range from 2 to 10). None. GCS-EM was computed in intubated patients on the day of extubation. The main outcome was extubation failure, defined as unplanned reintubation within 5 days of extubation. Analyses used multilevel logistic regression with adjustment for patient characteristics and a random intercept for hospital site. In the primary analysis, GCS-EM was not associated with extubation failure (odds ratio, 1.07 per additional point; 95% CI, 0.87-1.31). Findings were consistent in sensitivity analyses that: 1) used different adjustment covariates, 2) included a verbal estimate to derive an overall GCS, 3) accounted for missing data, 4) considered a 2-day time interval to define extubation failure, 5) accounted for competing risks, and 6) used a propensity score-based model. There was no association between GCS-EM and extubation outcome in subgroups defined by brain injury diagnosis or age. In this large, contemporary, multicenter cohort of patients with acute brain injury, we found no association between the GCS-EM and odds of extubation failure. However, few patients had a pre-extubation GCS-EM less than or equal to 8, and the possibility of a true prognostic association in patients with low scores is not excluded.
Chiara Robba, Denise Battaglini, Abbas Abbas, Ezequiel Sarrió, Raphael Cinotti, Karim Asehnoune, Fabio S. Taccone, Patricia R. Rocco, Marcus J. Schultz, Giuseppe Citerio, Robert David Stevens, Rafael Badenes, Paër-Sélim Abback, Anaïs Codorniu, Giuseppe Citerio, Vittoria Ludovica Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Jessica Giuseppina Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Chiara Robba, Denise Battaglini, Patrick Biston, Mohamed Fathi Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter van Vliet, Benjamin Marcel Gerretsen, Iris Xochitl Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, Wytze J. Vermeijden, Alexander Daniel Cornet, Sergio Infra Reyes Gard, Rafael Lara Cirino Domínguez, Maria Mercedes Bellini, Maria Gomez Milagros Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronial, Roberto Carlos Miranda-Ackerman, Francisco José Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Companion, David Pérez-Torres, Estefanía Prol-Silva, Hana Basheer Yahya, Ala Khaled, Mohamed Ghulam, Cracchiolo Neville Andrea, Palma Maria Daniela, Cristian Deana, Luigi Vetrugno, Manuel Rivera J. Chavez, Rocio Mendoza Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu der van Jagt, Job van Steenkiste, Hazem Ahmed, Alexander Edward Coombs, Jessie Welbourne, Ana Velarde Alicia Pineda, Víctor Nubert Hugo Castillo, Mohammed A. Azab, Ahmed Y. Azzam, David van Paul Michael Meenen, Gilberto Adrian Gasca, Alfredo Arellano, Forttino Galicia-Espinosa, José Carlos García-Ramos, Ghanshyam Yadav, Amarendra Kumar Jha, Vincent Robert-Edan, Pierre-Andre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Gilberto Adrian Gasca, Alfredo Arellano, Syed Tariq Reza, Md. Mozaffer Hossain, Christos Papadas, Vasiliki Chantziara, Chrysanthi Sklavou, Yannick Hourmant, Nicolas Grillot, Job van Steenkiste, Mathieu der van Jagt, Romain Pirracchio, Abdelraouf Akkari, Mohamed Abdelaty, Ahmed Hashim, Yoann Launey, Elodie Masseret, Sigismond Lasocki, Gergaud Soizic, Nicolas Mouclier, Sulekha Saxena, Avinash Agrawal, Shakti Bedanta Mishra, Samir Samal, Julio Cesar Mijangos, Mattias Haënggi, Mohan Gurjar, Marcus J. Schultz, Callum Kaye, Daniela Agustin Godoy, Pablo Alvarez, Aikaterini Ioakeimidou, Yoshitoyo Ueno, Rafael Badenes, Abdurrahmaan Suei Ali Elbuzidi, Michaël Piagnerelli, Muhammed Elhadi, Syed Tariq Reza, Mohammed Atef Azab, Jean Catherine Digitale, Nicholas Fong, Ricardo Campos Cerda, Norma Torre la de Peredo, Victoria McCredie, Elbuzidi Ali Abdurrahmaan Suei, Matthias Haenggi and Jaber Samir : Clinical practice and effect of carbon dioxide on outcomes in mechanically ventilated acute brain-injured patients: a secondary analysis of the ENIO study., Intensive Care Medicine, 50, 2, 234-246, 2024.
(Summary)
The use of arterial partial pressure of carbon dioxide (PaCO2) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO2 with in-hospital mortality. We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO2 > 35 and to 45 mmHg; mild hypocapnia as 32-35 mmHg; severe hypocapnia as 26-31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg. 1476 patients (65.9% male, mean age 52 <mml:mo>±</mml:mo> 18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO2 had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients. Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO2 values were significantly associated with increased in-hospital mortality.
Carolina Iaquaniello, Fabio Gallo, Raphael Cinotti, Giuseppe Citerio, S. Fabio Taccone, Paolo Pelosi, Rafael Badenes, Chiara Robba, Sélim Paër Abback, Anaïs Codorniu, Ludovica Vittoria Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Giuseppina Jessica Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Denise Battaglini, Patrick Biston, Fathi Mohamed Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter Vliet Van, Marcel Benjamin Gerretsen, Xochitl Iris Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, J. Wytze Vermeijden, Daniel Alexander Cornet, Reyes Sergio Inurrigarro, Lara Rafael Cirino Domínguez, Mercedes Maria Bellini, Gomez Maria Milagros Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Carlos Roberto Miranda-Ackerman, José Francisco Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Basheer Hana Yahya, Ala Khaled, Mohamed Ghula, Andrea Neville Cracchiolo, Daniela Maria Palma, Cristian Deana, Luigi Vetrugno, J. Chavez Manuel Rivera, Mendoza Rocio Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu Der Jagt Van, Job Steenkiste Van, Hazem Ahmed, Edward Alexander Coombs, Jessie Welbourne, Velarde Ana Alicia Pineda, Nubert Víctor Hugo Castillo, A. Mohammed Azab, Y. Ahmed Azzam, Paul Meenen David Michael Van, Adrian Gilberto Gasca, Alfredo Arellano, Forttino Galicia-Espinosa, Carlos José García-Ramos, Ghanshyam Yadav, Kumar Amarendra Jha, Vincent Robert-Edan, Andre Pierre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Adrian Gilberto Gasca, Alfredo Arellano, et al. and Yoshitoyo Ueno : The use of tier three therapies in acute brain injured patients: Insight from the Extubation strategies in Neuro-Intensive care unit patients and associations with Outcomes observational study, European Journal of Anaesthesiology and Intensive Care, 3, 1, e0043, 2024.
Natsumi Teshima, Kazuhito Matsuzaki, Noriya Enomoto, Masaaki Korai, Yoshitaka Kurashiki, Mami Hanaoka, Hitoshi Niki and Koichi Satoh : Case of Cerebrospinal Fluid Leakage Nine Years after Pituitary Gamma Knife Surgery for Poststroke Thalamic Pain Syndrome., NMC Case Report Journal, 10, 209-213, 2023.
(Summary)
Pituitary gamma knife surgery (GKS) is a treatment option for poststroke thalamic pain syndrome. Complications such as hypopituitarism, transient enuresis, and transient hyponatremia have been reported. However, cerebrospinal fluid (CSF) leakage has not yet been reported as a complication of pituitary GKS for poststroke thalamic pain syndrome. Herein, we report a case of delayed CSF rhinorrhea that developed 9 years after GKS for poststroke thalamic pain syndrome. A 64-year-old man presented to our hospital with bacterial meningitis and CSF rhinorrhea. Pituitary GKS for poststroke thalamic pain had been performed 9 years prior to his admission to our hospital. Computed tomography revealed pneumocephalus, fluid in the sphenoid and maxillary sinuses, and a partial bony defect of the sella turcica floor with communication between the paranasal and intracranial spaces. The CSF rhinorrhea resolved with bed rest and a lumbar CSF drain but recurred several days later. The patient underwent direct endoscopic surgical repair of the skull base. The sellar floor was covered with an autologous fascia graft harvested from the rectus sheath, and the sphenoid sinus was packed with abdominal fat grafts. The patient recovered, and the CSF rhinorrhea has not recurred for 2 years. Long-term follow-up is necessary after pituitary GKS, considering the complication of delayed CSF leakage.
Chiara Robba, Denise Battaglini, Raphael Cinotti, Karim Asehnoune, Robert Stevens, Fabio Silvio Taccone, Rafael Badenes, Paolo Pelosi, Paër-Sélim Abback, Anaïs Codorniu, Giuseppe Citerio, Vittoria Ludovica Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Jessica Giuseppina Maugeri, Bellissima Agrippino, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Mohamed Fathi Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter van Vliet, Benjamin Marcel Gerretsen, Iris Xochitl Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, Wytze J Vermeijden, Alexander Daniel Cornet, Sergio Reyes Inurrigarro, Rafael Lara Cirino Domínguez, Maria Mercedes Bellini, Maria Milagros Gomez-Haedo, Laura Lamot and et al. : Individualized Thresholds of Hypoxemia and Hyperoxemia and their Effect on Outcome in Acute Brain Injured Patients: A Secondary Analysis of the ENIO Study., Neurocritical Care, 40, 2, 515-528, 2023.
(Summary)
In acute brain injury (ABI), the effects of hypoxemia as a potential cause of secondary brain damage and poor outcome are well documented, whereas the impact of hyperoxemia is unclear. The primary aim of this study was to assess the episodes of hypoxemia and hyperoxemia in patients with ABI during the intensive care unit (ICU) stay and to determine their association with in-hospital mortality. The secondary aim was to identify the optimal thresholds of arterial partial pressure of oxygen (PaO2) predicting in-hospital mortality. We conducted a secondary analysis of a prospective multicenter observational cohort study. Adult patients with ABI (traumatic brain injury, subarachnoid aneurysmal hemorrhage, intracranial hemorrhage, ischemic stroke) with available data on PaO2 during the ICU stay were included. Hypoxemia was defined as PaO2 < 80 mm Hg, normoxemia was defined as PaO2 between 80 and 120 mm Hg, mild/moderate hyperoxemia was defined as PaO2 between 121 and 299 mm Hg, and severe hyperoxemia was defined as PaO2 levels ≥ 300 mm Hg. A total of 1,407 patients were included in this study. The mean age was 52 (±18) years, and 929 (66%) were male. Over the ICU stay, the fractions of patients in the study cohort who had at least one episode of hypoxemia, mild/moderate hyperoxemia, and severe hyperoxemia were 31.3%, 53.0%, and 1.7%, respectively. PaO2 values below 92 mm Hg and above 156 mm Hg were associated with an increased probability of in-hospital mortality. Differences were observed among subgroups of patients with ABI, with consistent effects only seen in patients without traumatic brain injury. In patients with ABI, hypoxemia and mild/moderate hyperoxemia were relatively frequent. Hypoxemia and hyperoxemia during ICU stay may influence in-hospital mortality. However, the small number of oxygen values collected represents a major limitation of the study.
Sarah Wahlster, Monisha Sharma, Shaurya Taran, A. James Town, D. Robert Stevens, Raphaël Cinotti, Karim Asehoune, Paolo Pelosi, Chiara Robba, sélim Paër Abback, Anaïs Codorniu, Giuseppe Citerio, Ludovica Vittoria Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Giuseppina Jessica Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Denise Battaglini, Patrick Biston, Fathi Mohamed Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter Vliet van, Marcel Benjamin Gerretsen, Xochitl Iris Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, J. Wytze Vermeijden, Daniel Alexander Cornet, Reyes Sergio Inurrigarro, Lara Rafael Cirino Domínguez, Mercedes Maria Bellini, Milagros Haedo Maria Gomez, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Carlos Roberto Miranda-Ackerman, José Francisco Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Basheer Hana Yahya, Ala Khaled, Mohamed Ghula, Neville Cracchiolo Andrea, Maria Palma Daniela, Cristian Deana, Luigi Vetrugno, J.Rivera Manuel Chavez, Mendoza Rocio Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu der Jagt van, Job Steenkiste van, Hazem Ahmed, Edward Alexander Coombs, Jessie Welbourne, Alicia Pineda Ana Velarde, Hugo Castillo Víctor Nubert, A. Mohammed Azab, Y. Ahmed Azzam, Paul Meenen David Michael van, Adrian Gilberto Gasca, Alfredo Arellano, Forttino Galicia-Espinosa, Carlos José García-Ramos, Ghanshyam Yadav, Kumar Amarendra Jha, Vincent Robert-Edan, Andre Pierre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal and Yashbir Deewan : Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial, Critical Care, 27, 1, 156, 2023.
(Summary)
There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale 12 before intubation) who required mechanical ventilation (MV) 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.
Hiroki TAKAI, Shodai YAMADA, Yoshihiro SUNADA, Yoshifumi TAO, Yukari MINAMI(OGAWA), Noriya Enomoto, Satoshi HIRAI, Kenji YAGI, Shunji MATSUBARA and Masaaki UNO : Surgical Approach to Remove a Central Venous Catheter Inserted into the Vertebral Artery: A Case Report, Surgery for Cerebral Stroke, 51, 3, 244-250, 2023.
Tomohiro Matsuda, Koichi Satoh, Takeshi Miyamoto, Noriya Enomoto, Mami Hanaoka, Hitoshi Niki and Kazuhito Matsuzaki : A case of ruptured dissecting posterior inferior cerebellar artery (PICA) aneurysm with double origin of the PICA avoiding ischemic complications, Japanese Journal of Stroke, 45, 6, 473-478, 2023.
Raphaël Cinotti, Cesar Julio Mijangos, Paolo Pelosi, Matthias Haenggi, Mohan Gurjar, J. Marcus Schultz, Callum Kaye, Agustin Daniel Godoy, Pablo Alvarez, Aikaterini Ioakeimidou, Yoshitoyo Ueno, Rafael Badenes, Ali Elbuzidi Abdurrahmaan Suei, Michaël Piagnerelli, Muhammed Elhadi, Tariq Syed Reza, Atef Mohammed Azab, Victoria McCredie, D. Robert Stevens, Catherine Jean Digitale, Nicholas Fong, Karim Asehnoune, sélim Paër Abback, Anaïs Codorniu, Giuseppe Citerio, Ludovica Vittoria Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Giuseppina Jessica Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Chiara Robba, Denise Battaglini, Patrick Biston, Fathi Mohamed Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter Vliet van, Marcel Benjamin Gerretsen, Xochitl Iris Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, J. Wytze Vermeijden, Daniel Alexander Cornet, Reyes Sergio Inurrigarro, Lara Rafael Cirino Domínguez, Mercedes Maria Bellini, Gomez Maria Milagros Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Carlos Roberto Miranda-Ackerman, José Francisco Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Basheer Hana Yahya, Ala Khaled, Mohamed Ghula, Neville Cracchiolo Andrea, Maria Palma Daniela, Cristian Deana, Luigi Vetrugno, J.Rivera Manuel Chavez, Mendoza Rocio Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu der Jagt van, Job Steenkiste van, Hazem Ahmed, Edward Alexander Coombs, Jessie Welbourne, Velarde Ana Alicia Pineda, Nubert Víctor Hugo Castillo and Atef Mohammed Azab : Extubation in neurocritical care patients: the ENIO international prospective study, Intensive Care Medicine, 48, 11, 1539-1550, 2022.
(Summary)
Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.
Noriya Enomoto, Kenji Yagi, Shunji Matsubara and Masaaki Uno : Case Report: Bow Hunter's Syndrome Caused by Compression of Extracranially Originated Posterior Inferior Cerebellar Artery., Frontiers in Neurology, 12, 2021.
(Summary)
Bow hunter's syndrome (BHS) is most commonly caused by compression of the vertebral artery (VA). It has not been known to occur due to an extracranially originated posterior inferior cerebellar artery (PICA), the first case of which we present herein. A 71-year-old man presented with reproducible dizziness on leftward head rotation, indicative of BHS. On radiographic examination, the bilateral VAs merged into the basilar artery, and the left VA was predominant. The right PICA originated extracranially from the right VA at the atlas-axis level and ran vertically into the spinal canal. During the head rotation that induced dizziness, the right PICA was occluded, and a VA stenosis was revealed. Occlusion of the PICA was considered to be the primary cause of the dizziness. The patient underwent surgery to decompress the right PICA and VA via a posterior cervical approach. Following surgery, the patient's dizziness disappeared, and the stenotic change at the right VA and PICA improved. The PICA could be a causative artery for BHS when it originates extracranially at the atlas-axis level, and posterior decompression is an effective way to treat it.
Shunji Matsubara, Hiroyuki Toi, Hiroki Takai, Yuko Miyazaki, Keita Kinoshita, Yoshihiro Sunada, Shodai Yamada, Yoshifumi Tao, Noriya Enomoto, Ogawa Yukari Minami, Satoshi Hirai, Kenji Yagi, Hiroyuki Nakashima and Masaaki Uno : Variations and management for patients with craniocervical junction arteriovenous fistulas: Comparison of dural, radicular, and epidural arteriovenous fistulas., Surgical Neurology International, 12, 2021.
(Summary)
Craniocervical junction arteriovenous fistulas (CCJAVFs) are known to be rare, but variations and clinical behaviors remain controversial.A total of 11 CCJAVF patients (M: F=9:2, age 54-77 years) were investigated. Based on the radiological and intraoperative findings, they were categorized into three types: dural AVF (DAVF), radicular AVF (RAVF), and epidural AVF (EDAVF).There were four symptomatic patients (subarachnoid hemorrhage in two, myelopathy in one, and tinnitus in one) and seven asymptomatic patients in whom coincidental CCJAVFs were discovered on imaging studies for other vascular diseases (arteriovenous malformation in one, intracranial DAVF in two, ruptured cerebral aneurysm in two, and carotid artery stenosis in two). Of these 11 patients, 2 (18.2%) had multiple CCJAVFs. Of 14 lesions, the diagnoses were DAVF in 5, RAVF in 3, and EDAVF in 6 (C1-C2 level ratio =5:0, 2:1, 3:3). Patients with DAVF/RAVF in four lesions with intradural venous reflux underwent surgery, although an RAVF remained in one lesion after embolization/radiation. Since all six EDAVFs, two DAVFs, and one RAVF had neither feeder aneurysms nor significant symptoms, no treatment was provided; of these nine lesions, one DAVF and one RAVF remained unchanged, whereas six EDAVFs showed spontaneous obliteration within a year. Unfortunately, however, one DAVF bled before elective surgery.CCJAVFs have many variations of shunting site, angioarchitecture, and multiplicity, and they were frequently associated with coincidental vascular lesions. For symptomatic DAVF/RAVF lesions with intradural drainage, surgery is preferred, whereas asymptomatic EDAVFs without dangerous drainage may obliterate during their natural course.
Noriya Enomoto, Kiyohito Shinno, Tetsuya Tamura, Eiji Shikata, Kenji Shono and Kensaku Takase : Ruptured Basilar Artery Perforator Aneurysm: A Case Report and Review of the Literature., NMC Case Report Journal, 7, 3, 93-100, 2020.
(Summary)
Basilar artery perforator aneurysms (BAPAs) are a rare cause of subarachnoid hemorrhage (SAH), and the natural history is still unknown. Herein, we report a case of ruptured BAPA that appeared during the observation period and then spontaneously disappeared; we have also conducted a review of the literature and performed an analysis based on the type of management. This case of BAPA had a unique course, and our observations may help establish a treatment strategy. A 60-year-old man presented with acute diffuse SAH, World Federation of Neurosurgical Societies (WFNS) Grade II and Fisher Grade 3. Initial three-dimensional digital subtraction angiography (DSA) did not show the source of the hemorrhage. DSA performed on day 39 showed a BAPA with a diameter of 3 mm at the posterior surface of the upper third of the basilar artery. Conservative treatment was chosen. DSA performed on day 64 showed complete resolution of the aneurysm. BAPAs are likely pseudoaneurysms, and not saccular aneurysms, caused due to dissection of basilar perforator arteries. BAPAs are often not recognized on initial imaging, and hence, it is necessary to repeat the DSA examination. Considering the relatively high rate of spontaneous resolution, we chose conservative management. When BAPAs enlarge or do not disappear after conservative treatment, additional therapy such as multiple stents should be considered.
Hideo Mure, Noriya Enomoto, Toshiyuki Okazaki, Shinya Okita and Shinji Nagahiro : A Case of Cerebrospinal Fluid Leak Associated with a Meningeal Diverticulum at the C2 Root Sleeve, Spinal Surgery, 33, 1, 85-87, 2019.
Noriya Enomoto, Hideo Mure, Toshiyuki Okazaki, Mai Azumi, S Okita, Shinji Nagahiro and Yasushi Takagi : Posttraumatic Cerebrospinal Fluid Leak Associated with an Upper Cervical Meningeal Diverticulum, World Neurosurgery, 116, 50-55, 2018.
(Summary)
Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear. We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved. Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak.
Hugues Courson de, Nicolas Massart, Karim Asehnoune, Raphaël Cinotti, sélim Paër Abback, Anaïs Codorniu, Giuseppe Citerio, Ludovica Vittoria Sala, Marinella Astuto, Eleonora Tringali, Daniela Alampi, Monica Rocco, Giuseppina Jessica Maugeri, Agrippino Bellissima, Matteo Filippini, Nicoletta Lazzeri, Andrea Cortegiani, Mariachiara Ippolito, Chiara Robba, Denise Battaglini, Patrick Biston, Fathi Mohamed Al-Gharyani, Russell Chabanne, Léo Astier, Benjamin Soyer, Samuel Gaugain, Alice Zimmerli, Urs Pietsch, Miodrag Filipovic, Giovanna Brandi, Giulio Bicciato, Ainhoa Serrano, Berta Monleon, Peter Vliet van, Marcel Benjamin Gerretsen, Xochitl Iris Ortiz-Macias, Jun Oto, Noriya Enomoto, Tomomichi Matsuda, Nobutaka Masui, Pierre Garçon, Jonathan Zarka, J. Wytze Vermeijden, Daniel Alexander Cornet, Reyes Sergio Inurrigarro, Lara Rafael Cirino Domínguez, Mercedes Maria Bellini, Gomez Maria Milagros Haedo, Laura Lamot, Jose Orquera, Matthieu Biais, Delphine Georges, Arvind Baronia, Carlos Roberto Miranda-Ackerman, José Francisco Barbosa-Camacho, John Porter, Miguel Lopez-Morales, Thomas Geeraerts, Baptiste Compagnon, David Pérez-Torres, Estefanía Prol-Silva, Basheer Hana Yahya, Ala Khaled, Mohamed Ghula, Neville Cracchiolo Andrea, Maria Palma Daniela, Cristian Deana, Luigi Vetrugno, J.Rivera Manuel Chavez, Mendoza Rocio Trujillo, Vincent Legros, Benjamin Brochet, Olivier Huet, Marie Geslain, Mathieu der Jagt van, Job Steenkiste van, Hazem Ahmed, Edward Alexander Coombs, Jessie Welbourne, Velarde Ana Alicia Pineda, Nubert Víctor Hugo Castillo, A. Mohammed Azab, Y. Ahmed Azzam, Paul Meenen David Michael van, Adrian Gilberto Gasca, Alfredo Arellano, Forttino Galicia-Espino-sa, Carlos José García-Ramos, Ghanshyam Yadav, Kumar Amarendra Jha, Vincent Robert-Edan, Andre Pierre Rodie-Talbere, Gaurav Jain, Sagarika Panda, Sonika Agarwal, Yashbir Deewan, Adrian Gilberto Gasca, Alfredo Arellano, Tariq Syed Reza and Mozaffer Md Hossain : Risk factors of extubation failure in neurocritical patients with the most impaired consciousness, Intensive Care Medicine, 49, 10, 1251-1253, 2023.
Noriya Enomoto, Takeshi Miyamoto, Hiroshi Koyama, Masaaki Korai, Yoshiteru Tada, Kenji Shimada, Kitazato Keiko and Yasushi Takagi : Lipopolysaccharide of periodontal bacteria influences the incidence of subarachnoid hemorrhage, Brain & Brain PET 2025, Seoul, Jun. 2025.
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Masaaki Korai, Noriya Enomoto, Takeshi Miyamoto, Kenji Shimada and Yasushi Takagi : Basic technique of carotid endarterectomy with patch graft and long- term outcomes at 10 and 15 years postoperatively, Brain & Brain PET 2025, Seoul, Jun. 2025.