Somatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. METHODS: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. RESULTS: We found that in mice expressing one of two common genetic drivers of meningioma - Pik3ca H1047R or AKT1 E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3ca H1074R and AKT1 E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin. CONCLUSIONS: In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).

Intracranial dural arteriovenous fistulas: association with cerebral venous thrombosis, baseline aggressiveness, and clinical outcomes. A retrospective multicenter study on 263 consecutive patients and literature review.

OBJECTIVE: The pathogenesis of intracranial dural arteriovenous fistulas (icDAVFs) is controversial. Cerebral vein thrombosis (CVT) and venous hypertension are recognized predisposing factors. This study aimed to evaluate the incidence of association between icDAVF and CVT and describe baseline aggressiveness and clinical outcomes for icDAVFs associated with CVT. The authors also performed a literature review of studies reporting icDAVF associated with CVT. METHODS: Two hundred sixty-three consecutive patients in two university hospitals with confirmed icDAVFs were included. A double-blind imaging review was performed to determine the presence or absence of CVT close or distant to the icDAVF. Location, type (using the Cognard classification), aggressiveness of the icDAVF, clinical presentation, treatment modality, and clinical and/or angiographic outcomes at 6 months were also collected. All prior brain imaging was analyzed to determine the natural history of onset of the icDAVF. RESULTS: Among the 263 included patients, 75 (28.5%) presented with a CVT concomitant to their icDAVF. For 18 (78.3%) of 23 patients with previous brain imaging available, CVT preceding the icDAVF was proven (6.8% of the overall population). Former/active smoking (OR 2.0, 95% CI 1.079-3.682, p = 0.022) and prothrombogenic status (active inflammation or cancer/coagulation trouble) were risk factors for CVT associated with icDAVF (OR 3.135, 95% CI 1.391-7.108, p = 0.003). One hundred eighty-seven patients (71.1%) had a baseline aggressive icDAVF, not linked to the presence of a CVT (p = 0.546). Of the overall population, 11 patients (4.2%) presented with spontaneous occlusion of their icDAVF at follow-up. Seven patients (2.7%) died during the follow-up period. Intracranial DAVF + CVT was not associated with a worse prognosis (modified Rankin Scale score at 3-6 months: 0 [interquartile range {IQR} 0-1] for icDAVF + CVT vs 0 [IQR 0-0] for icDAVF alone; p = 0.055). CONCLUSIONS: This was one of the largest studies focused on the incidence of CVT associated with icDAVF. For 6.8% of the patients, a natural history of CVT leading to icDAVF was proven, corresponding to 78.3% of patients with previous imaging available. This work offers further insights into icDAVF pathophysiology, aiding in identifying high-risk CVT patients for long-term follow-up imaging. Annual imaging follow-up using noninvasive vascular imaging (CT or MR angiography) for a minimum of 3 years after the diagnosis of CVT should be considered in high-risk patients, i.e., smokers and those with prothrombogenic status.

Corticosteroid treatment for refractory intracranial hypertension: a rescue therapy in patients with severe traumatic brain injury with contusional lesions-a feedback.

INTRODUCTION: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. METHODS: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. RESULTS: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). DISCUSSION: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries.

The Egyptian Escalator: Gaining access to distal parent vessel in giant and large aneurysms.

Flow-diverter stents have become the mainstay of endovascular treatment for giant and large intracranial aneurysms. However, the local aneurysmal hemodynamics, the incorporation of the parent vessel and the frequent wide-neck configuration render gaining stable distal parent artery access difficult. In this technical video, we present three cases in which we employed the so called "Egyptian Escalator technique" for obtaining and maintaining stable distal access: after looping the microwire and microcatheter inside the aneurysmal sac and exiting in the distal parent artery, we deployed a stent-retriever and utilized a gentle traction on the microcatheter in order to straighten the intra-aneurysmal loop. Afterwards, a flow-diverter stent was deployed, with optimal coverage of the aneurysmal neck. The "Egyptian Escalator" technique provides a useful approach for obtaining stable distal access for flow-diverter deployment in giant and large aneurysm (supplementary mmc1 (Video 1)).

Radial artery occlusion after aneurysm treatment using the rist guide catheter: Single center cohort study.

BACKGROUND AND PURPOSE: Delayed radial artery occlusion (dRAO) is a frequent complication after transradial access (TRA) for neurointervention when using standard large guide catheters. The RIST 079 guide catheter (RIST GC) is the first catheter designed for TRA in neurointervention. We aimed to assess the rate of dRAO after intracranial aneurysm (IA) treatment using the RIST GC. METHODS: Patients treated for an IA using TRA and the RIST GC between June 2021 and November 2022 were referred to a systematic US-doppler assessment of the radial artery patency at 3-month follow-up. Patients with and without dRAO were compared to identify risk factors. RESULTS: Twenty-two patients were included in the analysis. At 3-months follow up, 6 patients (27.3 %) presented with dRAO. Four patients were asymptomatic and 2 experienced post-operative radial hematoma and wrist pain. There was a tendency towards younger age, longer procedure duration and higher rate of forearm hematoma in patients with dRAO. Navigation using the RIST GC was successful in 90.9 % of cases. Intracranial access failures and navigation complications were all related to left internal carotid artery navigation. CONCLUSIONS: At 3-month follow up, 27.3 % of patients treated for IA using TRA with the RIST GC presented dRAO.

Brain Biopsy for Neurological Diseases of Unknown Etiology in Critically Ill Patients: Feasibility, Safety, and Diagnostic Yield.

OBJECTIVES: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context. DESIGN: Monocenter, retrospective, observational cohort study. SETTING: A French tertiary center. PATIENTS: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4-3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01-2.6]; p = 0.04). CONCLUSIONS: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.

Exclusion treatment of ruptured and unruptured low-grade brain arteriovenous malformations: a systematic review.

PURPOSE: To assess the obliteration rate, functional outcome, hemorrhagic complication, and mortality rates of exclusion treatment of low-grade brain arteriovenous malformations (BAVMs) (Spetzler and Martin grades (SMGs) 1 and 2), either ruptured or unruptured. METHODS: Electronic databases-Ovid MEDLINE and PubMed-were searched for studies in which there was evidence of exclusion treatment of low-grade BAVMs treated either by endovascular, surgical, radiosurgical, or multimodality treatment. The primary outcome of interest was angiographic obliteration post-treatment and at follow-up. The secondary outcomes of interest were functional outcome (mRS), mortality rate, and hemorrhagic complication. Descriptive statistics were used to calculate rates and means. RESULTS: Eleven studies involving 1809 patients with low-grade BAVMs were included. Among these, 1790 patients treated by either endovascular, surgical, radiosurgical, or multimodality treatment were included in this analysis. Seventy-two percent of BAVMs were Spetzler-Martin grade II. The overall (i.e., including all exclusion treatment modalities) complete obliteration rate ranged from 36.5 to 100%. The overall symptomatic hemorrhagic complication rate ranged from 0 to 7.3%; procedure-related mortality ranged from 0 to 4.7%. CONCLUSION: Our systematic review of the literature reveals a high overall obliteration rate for low-grade BAVMs, either ruptured or unruptured, with low mortality rate and an acceptable post-treatment hemorrhagic complication rate. These results suggest that exclusion treatment of low-grade BAVMs may be safe and effective, regardless of the treatment modality chosen.

Anterior interhemispheric approach for anterior fossa dural arteriovenous fistulas.

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion.

Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort.

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

Idiopathic Intracranial Hypertension: Glymphedema of the Brain.

BACKGROUND: During the last decade, our understanding of cerebrospinal fluid (CSF) physiology has dramatically improved, thanks to the discoveries of both the glymphatic system and lymphatic vessels lining the dura mater in human brains. EVIDENCE ACQUISITION: We detail the recent basic science findings in the field of CSF physiology and connect them with our current understanding of the pathophysiology of idiopathic intracranial hypertension (IIH). RESULTS: Transverse sinus (TS) stenoses seem to play a major causative role in the symptoms of IIH, as a result of a decrease in the pressure gradient between the venous system and the subarachnoid space. However, the intracranial pressure can be highly variable among different patients, depending on the efficiency of the lymphatic system to resorb the CSF and on the severity of TS stenoses. It is likely that there is a subclinical form of IIH and that IIH without papilledema is probably under-diagnosed among patients with chronic migraines or isolated tinnitus. CONCLUSIONS: IIH can be summarized in the following pathological triad: restriction of the venous CSF outflow pathway-overflow of the lymphatic CSF outflow pathway-congestion of the glymphatic system. To better encompass all the stages of IIH, it is likely that the Dandy criteria need to be updated and that perhaps renaming IIH should be considered.

Management of pituicytomas: a multicenter series of eight cases.

PURPOSE: Pituicytomas and spindle cell oncocytomas (SCOs) are two rare neoplasms of the sellar and suprasellar region, known to be challenging as they are extremely vascular and almost always misdiagnosed, altering our surgical planning and the patients' outcomes. Also we argue that recent update concerning the pathology findings of these tumors should be more widely generalized to our practice. METHODS: This is a retrospective multicenter study, reporting the clinical manifestations, radiological characteristics, histopathological features, treatment strategies and long-term outcomes of patients who have been treated for a Pituicytoma at various institutions in Paris, France over the past 10 years. In addition, we compared our results to the world literature in order to identify similarities concerning the radiographic diagnosis and the treatment strategies of these tumors. RESULTS: Eight patients were operated on in four different hospitals. Misdiagnosis was constant before surgery, pituitary adenoma or craniopharyngioma being suspected. During surgery (transsphenoidal approach: six cases, transcranial approach: two cases) unusual tumors were noted, with important bleeding in most cases. Complete resection could be obtained in five patients. Pathological diagnosis was confirmed in all cases. During the follow up two recurrences occurred. One was subsequently treated with radiotherapy, the other underwent a second surgery. CONCLUSION: Recent updates concerning the histological diagnosis of pituicytomas should be generalized to our practice in order to provide a better understanding of this rare pathology and its natural course.

Diffuse midline skull base meningiomas: identification of a rare and aggressive subgroup of meningiomas.

Skull base meningiomas may present as clinically aggressive tumors despite being histologically benign. Here we describe a clinico-radiological entity of diffuse midline skull base meningiomas responsible for several neurological morbidities, including hearing and vision loss, intracranial hypertension, secondary hydrocephalus and tonsillar herniation with spinal cord compression. Surgery and radiotherapy were ineffective in stopping the clinical course of those tumors. After targeted sequencing of known mutated genes in meningiomas, we discovered TRAF7 mutations in two out of four tumors, stressing the importance of focusing the research efforts of the meningioma community in understanding the mechanisms underlying TRAF7 related meningioma tumorigenesis.

Risk factors for angiographic recurrence after treatment of unruptured intracranial aneurysms: Outcomes from a series of 178 unruptured aneurysms treated by regular coiling or surgery.

BACKGROUND: Long-term stability after intracranial aneurysm exclusion by coiling is still a matter of debate; after surgical clipping little is known. OBJECTIVE: To study outcome after endovascular and surgical treatments for unruptured intracranial aneurysms in terms of short- and long-term angiographic exclusion and risk factors for recanalization. METHODS: From 2004 and 2009, patients treated for unruptured berry intracranial aneurysms by coiling or clipping were reviewed. Aneurysmal exclusion was evaluated using the Roy-Raymond grading scale; immediate clinical outcome was also assessed. Clinical outcome, recanalization, risk factors for recurrence and bleeding during the follow-up period were analyzed by groups; "surgery" and "embolization". RESULTS: From 2004 to 2009, 178 consecutive unruptured aneurysms were treated. The post-procedure angiographic results for "surgery" were: total exclusion 75.6%; residual neck 13.5%; residual aneurysm 10.8%. For "embolization", the results were, respectively: 72%; 20.7%; and 7.2%. Morbidity was 3% for "surgery" and 1.6% for "embolization" (P=0.74); mortality was nil. Mean clinical and angiographic follow-up was 5years. Recurrence rate was of 11.5% for "surgery" vs. 44% for "embolization" with a mean follow-up of 4 and 5.75years, respectively (P=1.10-5). The retreatment rate was 8.4%. Two significant risk factors for recanalization were identified: maximum diameter of the aneurysm sac (P=0.0038) and pericallosal location (P=0.0388). No bleeding event occurred. CONCLUSION: Both techniques are safe. The rate of aneurismal recurrence was significantly higher for embolization, especially for large diameter aneurysms and pericallosal locations. No bleeding event occurred after recanalization.

Patterns of relapse and growth kinetics of surgery- and radiation-refractory meningiomas.

Patients with surgery- and radiation-refractory meningiomas have a poor outcome. Due to our lack of knowledge concerning multi-recurrent meningioma natural history, their clinical course is poorly defined. This retrospective study aims at defining patterns of relapse in order to help in the definition of response criteria in future clinical trials. We performed a retrospective review of surgery- and radiotherapy-refractory meningioma cases with interpretable radiological follow-up treated in our department. Tumor volumes were measured on 3D T1 Gadolinium volumetric sequences using a semi-automated algorithm for tumor segmentation. Twenty nine patients with multi-treated meningioma (11 WHO Grade II, 5 de novo WHO Grade III and 13 transformed WHO Grade III), were evaluated. Median PFS was 16 months for patients with Grade II meningiomas. In patients with Grade III meningiomas, the de novo subgroup had a median PFS of 4 months compared with 7 months in patients with malignant transformation. Volumetric analysis of tumor growth concerned 95 tumor nodules in 50 relapses. The mean growth rate of tumor nodules was 10.4 cm(3)/year (95% CI 7.3-14.8 cm(3)/year). Three patterns of tumor growth were described: "classical" for 9 (31%) patients, "local multi-nodular" for 6 (21%) patients and "multi-nodular metastatic" for the last 14 (48%) patients. Considering all tumor nodules, median time to tumor progression (TTP) was 3.7 months. Progressing tumors represent the most frequent histological subgroup of surgery and radiation-refractory meningiomas while tumors with multi-nodular metastatic dissemination are the prominent radiological pattern of progression.

Recovery from oculomotor nerve palsy due to posterior communicating artery aneurysms: results after clipping versus coiling in a single-center series.

BACKGROUND: Oculomotor nerve palsy (ONP) is a common clinical manifestation of ruptured or unruptured posterior communicating artery (PcomA) aneurysms. Although microsurgical clip ligation has been proven a safe and durable treatment, endovascular management is emerging as an increasingly popular alternative. The aim of our study is to compare the recovery rate from ONP and assess the safety and long-term durability of both techniques. METHODS: We have reviewed the retrospective data concerning twenty-two patients treated at our institution between 2004 and 2012 for PcomA aneurysms with ONP. Seven patients were operated on via a standard pterional approach, and fourteen were treated by endovascular occlusion with coils. One patient was managed conservatively. Pre-treatment and post-treatment severity of ONP was recorded, as well as the duration of symptoms before admission and treatment-related complications. RESULTS: All seven patients who underwent surgery improved, with six total recoveries and one partial recovery. Among the fourteen patients treated by embolization, thirteen initially recovered, but long-term follow-up revealed three cases of exacerbation of ONP after refilling of the aneurysms. Two of them were clipped, and one embolized. Also, one partially resolved patient underwent a second embolization. No severe complications occurred in either group. CONCLUSIONS: Despite the small number of patients, our study suggests that both surgical clipping and embolization are safe and effective methods in regards to functional recovery (complete ONP recovery in about 85 % of the cases). However, coiling may lead to delayed recurrence of third cranial nerve (CN) palsy at long-term follow-up, requiring additional treatment.

KDM1A genotyping and expression in 146 sporadic somatotroph pituitary adenomas.

IMPORTANCE: A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism. OBJECTIVE: We aimed to analyze KDM1A gene sequence and KDM1A and GIPR expressions in somatotroph pituitary adenomas. SETTINGS: We conducted a cohort study at university hospitals in France and in Italy. We collected pituitary adenoma specimens from acromegalic patients who had undergone pituitary surgery. We performed targeted exome sequencing (gene panel analysis) and array-comparative genomic hybridization on somatic DNA derived from adenomas and performed droplet digital PCR on adenoma samples to quantify KDM1A and GIPR expressions. RESULTS: One hundred and forty-six patients with sporadic acromegaly were studied; 72.6% presented unsuppressed classical GH response, whereas 27.4% displayed a paradoxical rise in GH after oral glucose load. We did not identify any pathogenic variant in the KDM1A gene in the adenomas of these patients. However, we identified a recurrent 1p deletion encompassing the KDM1A locus in 29 adenomas and observed a higher prevalence of paradoxical GH rise (P = .0166), lower KDM1A expression (4.47 ± 2.49 vs 8.56 ± 5.62, P < .0001), and higher GIPR expression (1.09 ± 0.92 vs 0.43 ± 0.51, P = .0012) in adenomas from patients with KDM1A haploinsufficiency compared with those with 2 KDM1A copies. CONCLUSIONS AND RELEVANCE: Unlike in GIP-dependent primary bilateral macronodular adrenal hyperplasia, KDM1A genetic variations are not the cause of GIPR expression in somatotroph pituitary adenomas. Recurrent KDM1A haploinsufficiency, more frequently observed in GIPR-expressing adenomas, could be responsible for decreased KDM1A function resulting in transcriptional derepression on the GIPR locus.

Non-invasive ultrasonic surgery of the brain in non-human primates.

High-intensity focused ultrasound causes selective tissue necrosis efficiently and safely, namely, in the prostate, liver, and uterine fibroid. Nevertheless, ablation of brain tissue using focused ultrasound remains limited due to strong aberrations induced by the skull. To achieve ultrasonic transcranial brain ablation, such aberrations have to be compensated. In this study, non-invasive therapy was performed on monkeys using adaptive correction of the therapeutic beam and 3D simulations of transcranial wave propagation based on 3D computed tomographic (CT) scan information. The aim of the study was two-fold: induce lesions in a non-human primate brain non-invasively and investigate the potential side effects. Stereotactic targeting was performed on five Macaca fascicularis individuals. Each hemisphere was treated separately with a 15-day interval and animals were sacrificed two days after the last treatment. The ultrasonic dose delivered at the focus was increased from one treatment location to the other to estimate the thermal dose for tissue alteration. Thermal doses in the brain were determined by numerical computations. Treatment efficiency and safety were evaluated histologically. The threshold for tissue damage in the brain was measured to be between 90 and 280 cumulative equivalent minutes at 43 °C. Intravenous injection of corticoids before the treatment limited the side effects.

'Balloon pressure technique' for endovascular treatment of spinal cord arteriovenous fistulas: preliminary results in 10 cases.

BACKGROUND: Spinal arteriovenous fistulas (SAVFs) are challenging lesions to treat by endovascular means. Our purpose was to report our early experience with dual lumen balloons (DLBs) for embolization of SAVFs using ethylene vinyl alcohol (EVOH) (the so-called 'balloon pressure technique' (BPT)). MATERIALS AND METHODS: During the inclusion period, 10 consecutive patients (nine men, mean age 61.6 years) underwent endovascular treatment of a SAVF (seven dural SAVFs and three epidural SAVFs) at a single institution using the BPT. DLBs were used in all cases. In seven cases (70%), a regular DLB was used, while in three cases (30%), low profile DLBs were used. EVOH was used as the liquid embolic agent in all cases. Technical and clinical complications were systematically recorded. Clinical and angiographic outcomes were systematically evaluated more than 3 months after the procedure. RESULTS: Complete cure of the SAVF by endovascular means alone was obtained in 80% of cases (8/10). For the two patients with incomplete SAVF occlusion, surgery was successfully performed secondarily. No recurrence was found at the 3 month follow-up in the eight patients for whom complete occlusion was obtained at the end of the embolization procedure. No permanent clinical complication was recorded using the BPT. Clinical improvement was observed in 6/10 (60%) cases. CONCLUSION: BPT was a feasible technique, with regular or low profile DLBs, for embolization of SAVFs. Our preliminary results suggest the safety and effectiveness of this technique.

Balloon Pressure Technique with the Scepter Mini Balloon as Part of the Endovascular Strategy for Brain Arteriovenous Malformations Embolization : Preliminary Multicenter Experience.

BACKGROUND: The balloon pressure technique (BPT) is an alternative to the pressure cooker technique. A dual lumen balloon (DLB) is used to inject the liquid embolic agent through the working lumen while the balloon is inflated. The purpose of our study was to report our early experience using the Scepter Mini dual lumen balloons for BPT in brain arteriovenous malformation (bAVM) embolization. MATERIAL AND METHODS: Consecutive patients treated from July 2020 to July 2021 in 3 tertiary centers using the BPT with low-profile dual lumen balloons (Scepter Mini, Microvention, Tustin, CA, USA) by endovascular means for bAVMs were retrospectively reviewed. Patient demographics and bAVM angio-architectural features were collected. The feasibility of Scepter Mini balloon navigation close to the nidus was evaluated. Technical as well as clinical (ischemic and/or hemorrhagic) complications were also systematically assessed. The occlusion rate was evaluated on follow-up DSA. RESULTS: A total of 19 patients (10 females; mean age = 38.2 years) consecutively treated for a bAVM (8 ruptured/11 unruptured) using the BPT with a Scepter Mini through 23 embolization sessions were included in our series. Navigation of the Scepter Mini was feasible in all cases. Of the patients 3 (16%) had procedure-related ischemic stroke and 2 patients (10.5%) had late hemorrhages. None of these complications led to severe permanent sequela. Complete occlusion of bAVM embolized with intention to cure was recorded in 11/13 cases (84.6%). CONCLUSION: The BPT using low-profile dual lumen balloons is feasible and seems safe for embolization of bAVMs. It may help to reach high occlusion rates, especially when performed in the intent to cure by embolization only.