Surgery versus endovascular treatment for spinal dural arteriovenous fistulas: a multicenter experience and systematic literature review.

Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications.

Extended endoscopic transsphenoidal approach for suprasellar craniopharyngiomas.

BACKGROUND: Craniopharyngiomas are benign sellar lesions. Surgical excision of craniopharyngiomas is difficult because of the surrounding important neurovascular structures. The choice of surgery depends on the histological type, location, hormonal status, and size of the craniopharyngioma, surrounding neurovascular structures, and invasion of the brain parenchyma. METHODS: We describe the resection of an adamantinomatous craniopharyngioma using an extended endoscopic endonasal approach and discuss the relevant surgical anatomy, indications, limitations, and possible complications. CONCLUSIONS: The extended endoscopic endonasal approach allows successful removal of the craniopharyngioma and poses little risk to surrounding neurovascular structures.

How I do it: epidural transposition of the temporoparietal fascia flap for anterior skull base reconstruction.

BACKGROUND: Multilayer closures and the use of vascularized flaps have been showed to be very effective in the reconstruction of the anterior skull base (ASB) after extended endonasal approaches resulting in large bone and dural defects. In the case of unavailability of a local flap, regional ones like the temporoparietal fascia flap (TPFF), used until now via a transpterygoïd route (Bolzoni Villaret et al. in Eur Arch Otorhinolaryngol 270(4):1473-1479, 2023; Fortes et al. in Laryngoscope 117(6):970-976, 2017; Veyrat et al. in Acta Neurochir (Wien) 158(12):2291-2294, 2016), can be an effective alternative. METHOD: We describe a step-by-step technique of TPFF transposition via an epidural supraorbital corridor for the reconstruction of a large midline ASB defect. CONCLUSION: TPFF is a promising alternative for the reconstruction of the ASB defects.

Learning curve and influencing factors of performing microsurgical anastomosis: a laboratory prospective study.

Despite being a critical component of any cerebrovascular procedure, acquiring skills in microsurgical anastomosis is challenging for trainees. In this context, simulation models, especially laboratory training, enable trainees to master microsurgical techniques before performing real surgeries. The objective of this study was to identify the factors influencing the learning curve of microsurgical training. A prospective observational study was conducted during a 7-month diploma in microsurgical techniques carried out in the anatomy laboratory of the school of surgery. Training focused on end-to-end (ETE) and end-to-side (ETS) anastomoses performed on the abdominal aorta, vena cava, internal carotid and jugular vein, femoral artery and vein, caudal artery, etc. of Wistar strain rats under supervision of 2 expert anatomical trainers. Objective and subjective data were collected after each training session. The 44 microsurgical trainees enrolled in the course performed 1792 anastomoses (1577 ETE, 88%, vs. 215 ETS, 12%). The patency rate of 41% was independent from the trainees' surgical background and previous experience. The dissection and the temporary clamping time both significantly decreased over the months (p < 0.001). Technical mistakes were independently associated with thrombosis of the anastomoses, as assessed by the technical mistakes score (p < 0.01). The training duration (in weeks) at time of each anastomosis was the only significant predictor of permeability (p < 0.001). Training duration and technical mistakes constituted the two major factors driving the learning curve. Future studies should try and investigate other factors (such as access to wet laboratory, dedicated fellowships, mentoring during early years as junior consultant/attending) influencing the retention of surgical skills for our difficult and challenging discipline.

Correction to: A rare presentation of skull-base osteomyelitis with neurovascular sheath extension following external otitis resolved by PET/MRI.

The figure in the original published version of this article was omitted.

The lucent (CT) and enhancing (MR) rim, a sign of Paget's disease of the skull: case report.

Osteoporosis circumscripta is sometimes observed at the skull vault and corresponds to the initial stage of Paget's disease of the bone. Differentiating osteoporosis circumscripta from other reasons for osteolytic images of the vault may be difficult. We report a case of osteoporosis circumscripta of the frontal bone. A lucent rim seen on CT scan, which was enhanced on gadolinium-enhanced MRI, delineated the abnormal bone. The patient was a 50-year-old woman who had CT scans of the skull for chronic sinusitis. Pathology examination showed typical bone changes of Paget's disease. The lucent and enhancing rim sign may help in differentiating Paget's disease from other conditions.

Treatment of cerebral vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis.

OBJECTIVES: To examine the clinical outcome of aneurysmal subarachnoid haemorrhage (aSAH) patients exposed to cerebral vasospasm (CVS)-targeted treatments in a meta-analysis and to evaluate the efficacy of intra-arterial (IA) approaches in patients with severe/refractory vasospasm. METHODS: Randomised controlled trials, prospective and retrospective observational studies reporting clinical outcomes of aSAH patients exposed to CVS targeted treatments, published between 2006-2016 were searched using PubMed, EMBASE and the Cochrane Library. The main endpoint was the proportion of unfavourable outcomes, defined as a modified Rankin score of 3-6 at last follow-up. RESULTS: Sixty-two studies, including 26 randomised controlled trials, were included (8,976 patients). At last follow-up 2,490 of the 8,976 patients had an unfavourable outcome, including death (random-effect weighted-average, 33.7%; 99% confidence interval [CI], 28.1-39.7%; Q value, 806.0; I 2 = 92.7%). The RR of unfavourable outcome was lower in patients treated with Cilostazol (RR = 0.46; 95% CI, 0.25-0.85; P = 0.001; Q value, 1.5; I 2 = 0); and in refractory CVS patients treated by IA intervention (RR = 0.68; 95% CI, 0.57-0.80; P < 0.0001; number needed to treat with IA intervention, 6.2; 95% CI, 4.3-11.2) when compared with the best available medical treatment. CONCLUSIONS: Endovascular treatment may improve the outcome of patients with severe-refractory vasospasm. Further studies are needed to confirm this result. KEY POINTS: • 33.7% of patients with cerebral Vasospasm following aneurysmal subarachnoid-hemorrhage have an unfavorable outcome. • Refractory vasospasm patients treated using endovascular interventions have lower relative risk of unfavourable outcome. • Subarachnoid haemorrhage patients with severe vasospasm may benefit from endovascular interventions. • The relative risk of unfavourable outcome is lower in patients treated with Cilostazol.

PSMA-targeted bispecific Fab conjugates that engage T cells.

Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity.

Discovery of Pyrophosphate Diesters as Tunable, Soluble, and Bioorthogonal Linkers for Site-Specific Antibody-Drug Conjugates.

As part of an effort to examine the utility of antibody-drug conjugates (ADCs) beyond oncology indications, a novel pyrophosphate ester linker was discovered to enable the targeted delivery of glucocorticoids. As small molecules, these highly soluble phosphate ester drug linkers were found to have ideal orthogonal properties: robust plasma stability coupled with rapid release of payload in a lysosomal environment. Building upon these findings, site-specific ADCs were made between this drug linker combination and an antibody against human CD70, a receptor specifically expressed in immune cells but also found aberrantly expressed in multiple human carcinomas. Full characterization of these ADCs enabled procession to in vitro proof of concept, wherein ADCs 1-22 and 1-37 were demonstrated to afford potent, targeted delivery of glucocorticoids to a representative cell line, as measured by changes in glucocorticoid receptor-mediated gene mRNA levels. These activities were found to be antibody-, linker-, and payload-dependent. Preliminary mechanistic studies support the notion that lysosomal trafficking and enzymatic linker cleavage are required for activity and that the utility for the pyrophosphate linker may be general for internalizing ADCs as well as other targeted delivery platforms.

Novel Phosphate Modified Cathepsin B Linkers: Improving Aqueous Solubility and Enhancing Payload Scope of ADCs.

In an effort to examine the utility of antibody-drug conjugates (ADCs) beyond oncology indications, a novel phosphate bridged Cathepsin B sensitive linker was developed to enable the targeted delivery of glucocorticoids. Phosphate bridging of the Cathepsin B sensitive linkers allows for payload attachment at an aliphatic alcohol. As small molecule drug-linkers, these aqueous soluble phosphate containing drug-linkers were found to have robust plasma stability coupled with rapid release of payload in a lysosomal environment. Site-specific ADCs were successfully made between these drug-linkers and an antibody against human CD70, a receptor specifically expressed in immune cells but also found aberrantly expressed in multiple human carcinomas. These ADCs demonstrated in vitro targeted delivery of glucocorticoids to a representative cell line as measured by changes in glucocorticoid receptor (GR) mediated gene mRNA levels. This novel linker expands the scope of potential ADC payloads by allowing an aliphatic alcohol to be a stable, yet cleavable attachment site. This phosphate linker may have broad utility for internalizing ADCs as well as other targeted delivery platforms.

How I do it. The pedicled temporoparietal fascia flap for skull base reconstruction after endonasal endoscopic approaches.

BACKGROUND: Endoscopic endonasal approaches (EEA) are an alternative for removing challenging nasopharyngeal or skull base lesions. In some cases, a nasoseptal flap (NSF) is not always available and such complex procedures may lead to carotid arteries exposition and/or dura mater (DM) wide opening. Meticulous carotid coverage and DM reconstruction are crucial for preventing early and delayed complications. METHOD: We propose a step-by-step description of the pedicled temporoparietal fascia flap (TPFF) technique, with a focus on its pitfalls, advantages and limits. CONCLUSION: The TPFF is a reliable flap for skull base reconstruction when other pedicled flaps are not available. KEY POINTS: 1. Reliable flap even for irradiated patients 2. CT angiography with 3D reconstruction as pre-operative imaging 3. Doppler ultrasound probe to draw the artery's trajectory on skin 4. TPFF elevation concomitantly to the endoscopic procedure 5. Hemicoronal incision sufficient to harvest the TPFF 6. Superficial dissection in a plane just beneath the hair follicles 7. Dissection plane deep to the fad pad to preserve the frontal branch of the facial nerve 8. Surgical corridor wide enough to avoid any compression of the pedicle 9. Double visualization to avoid any twist and Doppler control of the STA patency 10. Close follow-up, toilet in clinics.

Elaboration of a semi-automated algorithm for brain arteriovenous malformation segmentation: initial results.

OBJECTIVES: The purpose of our study was to distinguish the different components of a brain arteriovenous malformation (bAVM) on 3D rotational angiography (3D-RA) using a semi-automated segmentation algorithm. MATERIALS AND METHODS: Data from 3D-RA of 15 patients (8 males, 7 females; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. Segmentation was performed in two steps: (1) nidus segmentation from propagation (vertical then horizontal) of tagging on the reference slice (i.e., the slice on which the nidus had the biggest surface); (2) contiguity propagation (based on density and variance) from tagging of arteries and veins distant from the nidus. Segmentation quality was evaluated by comparison with six frame/s DSA by two independent reviewers. Analysis of supraselective microcatheterisation was performed to dispel discrepancy. RESULTS: Mean duration for bAVM segmentation was 64 ± 26 min. Quality of segmentation was evaluated as good or fair in 93% of cases. Segmentation had better results than six frame/s DSA for the depiction of a focal ectasia on the main draining vein and for the evaluation of the venous drainage pattern. CONCLUSION: This segmentation algorithm is a promising tool that may help improve the understanding of bAVM angio-architecture, especially the venous drainage. KEY POINTS: • The segmentation algorithm allows for the distinction of the AVM's components • This algorithm helps to see the venous drainage of bAVMs more precisely • This algorithm may help to reduce the treatment-related complication rate.

Sporadically second localization of cerebellar hemangioblastoma in sella turcica mimicking a meningioma with no associated von Hippel-Lindau disease.

A 72-year-old man presented with a gradual bilateral decrease in visual acuity. Imaging showed lesion in the sella turcica diagnosed as meningioma but proving secondarily to be a hemangioblastoma. His neurosurgical history included a resection of a cerebellar hemangioblastoma 30 years ago. To our knowledge, such a hemangioblastoma second localization from the infratentorial to supratentorial has not been reported in the literature for patients not presenting with von Hippel-Lindau disease.

Subarachnoid hemorrhage induces an early and reversible cardiac injury associated with catecholamine release: one-week follow-up study.

INTRODUCTION: The occurrence of cardiac dysfunction is common after subarachnoid hemorrhage (SAH) and was hypothesized to be related to the release of endogenous catecholamines. The aim of this prospective study was to evaluate the relationship between endogenous catecholamine and cardiac dysfunction at the onset and during the first week after SAH. METHODS: Forty consecutive patients admitted for acute SAH without known heart disease were included. Catecholamine plasma concentrations and transthoracic echocardiography (TTE) were documented on admission, on day 1 (D1), and day 7 (D7). RESULTS: At baseline, 24 patients had a World Federation of Neurosurgical Societies score (WFNS) of one or two; the remaining 16 had a WFNS between three and five. Twenty patients showed signs of cardiac dysfunction on admission, including six with left ventricle (LV) systolodiastolic dysfunction and 14 with pure LV diastolic dysfunction. On admission, norepinephrine, epinephrine, dopamine, B-type Natriuretic Peptide (BNP) and Troponin Ic (cTnI) plasmatic levels were higher in patients with the higher WFNS score and in patients with altered cardiac function (all P <0.05). Among patients with cardiac injury, heart function was restored within one week in 13 patients, while seven showed persistent LV diastolic dysfunction (P = 0.002). Plasma BNP, cTnI, and catecholamine levels exerted a decrease towards normal values between D1 and D7. CONCLUSION: Our findings show that cardiac dysfunction seen early after SAH was associated with both a rapid and sustained endogenous catecholamine release and WFNS score. SAH-induced cardiac dysfunction was regressive over the first week and paralleled the normalization of catecholamine concentration.

Endoscopic endonasal approach in the management of skull base chordomas--clinical experience on a large series, technique, outcome, and pitfalls.

Skull base chordomas represent very interesting neoplasms, due to their rarity, biological behavior, and resistance to treatment. Their management is very challenging. Recently, the use of a natural corridor, through the nose and the sphenoid sinus, improved morbidity and mortality allowing also for excellent removal rates. Prospective analysis of 54 patients harboring a skull base chordoma that were managed by extended endonasal endoscopic approach (EEA). Among the 54 patients treated (during a 72 months period), 21 were women and 33 men, undergoing 58 procedures. Twenty-two cases (40%) were recurrent and 32 (60%) newly diagnosed chordomas. Among the 32 newly diagnosed chordomas, a gross total resection was achieved in 28 cases (88%), a near total (>95% of tumor) in 2 cases (6%), a partial (>50% of tumor) in 2 cases (6%). Among the 22 recurrent chordomas, resection was complete in 7 cases (30%), near total in 7 (30%), and partial in 8 (40%). The global gross total resection rate was 65% (35/54 cases). Four patients (11%) recurred and 4 (11%) progressed within a mean follow-up of 34 months (range 12-84 months). Four patients (11%) were re-operated; one patient (1.8%) died due to disease progression, one patient (1.8%) died 2 weeks after surgery due to a massive bleeding from an ICA pseudo aneurysm. CSF leakage occurred in four patients (8%), and meningitis in eight cases (14%). No new permanent neurological deficit occurred. The EEA management of skull base chordomas requires a long and gradual learning curve that once acquired offers the possibility of either similar or better resection rates as compared to traditional approaches while morbidity is improved.

Critical analysis of recurrences of esthesioneuroblastomas: can we prevent them?

Esthesioneuroblastoma (ENB) involving the anterior skull base is a rare malignant tumour derived from the olfactory epithelium. The gold standard of surgical treatment is currently craniofacial resection (CFR), which allows efficient removal of the tumour but entails significant morbidity. To reduce morbidity combined with good visualization of tumour limits removal, endonasal endoscopy resection (EER) has developed. The objective of this work was (1) to describe the EER surgical procedure, the morbidity, and the limitations of this endoscopic approach as compared with CFR, (2) analyse recurrences to define risk factors of recurrences and (3) to discuss a therapeutic decision algorithm. Retrospective series of 18 patients with ENB endoscopically treated in a university tertiary referral centre over 13 years. Fifteen of those underwent radiotherapy. Epidemiological data, clinical and imaging findings, histology, treatment modalities and outcome of patients were studied. Mean follow-up was 31 months. Morbidity was mainly related to radiotherapy. Three recurrences were detected: one bone and one sylvian metastasis, and a local recurrence in a patient not irradiated. One recurrence spread through leptomeningeal propagation. Dural extension and frontal invasion were significantly associated with recurrences (p = 0.001 and p = 0.019, respectively). Patients with dural extension or frontal invasion should receive aggressive treatment. With a low rate of perioperative morbidity and efficient local control, EER seems to be a promising approach for selected cases of ENB.

Causative role of infection in chronic non-thromboembolic pulmonary hypertension following ventriculo-atrial shunt.

A severe complication of ventriculo-atrial (VA) shunt placement for treatment of hydrocephalus is chronic thromboembolic pulmonary hypertension (CTEPH). We report here a patient with a VA shunt for treatment of hydrocephalus who presented two consecutive episodes of VA shunt-induced infection by Staphylococcus epidermidis and who rapidly developed chronic PH. Extensive radiological investigations and normal ventilation/perfusion lung scan allowed us to rule out CTEPH. To our knowledge, no other case of chronic pulmonary hypertension (PH) related to VA shunt insertion has been reported so far. PH in this patient with VA shunt is clinically distinct from CTEPH and has been caused by VA shunt-induced S. epidermidis infection per se.

The "Gift Wrap" Technique - A Method that Simplifies the Placement of Fascia Lata in the Reconstruction of the Skull Base Following Endoscopic Endonasal Surgery: A Technical Note.

BACKGROUND: With the advancement of endoscopic endonasal surgery in the treatment of anterior skull base (ASB) pathologies, extended, watertight reconstructions are needed to prevent cerebrospinal fluid (CSF) leakage. This often involves the use of multilayers closure, with free fascia lata (FL) graft frequently used as an in- and/or outlay. However, positioning the FL properly can be challenging and time-consuming, particularly on wider defects. In this technical note, we present an easier and faster way to position FL using a silicone sheet. METHODS: FL graft is harvested using a standard technique. The required dimensions are evaluated depending on the extent of the dural defect taking in consideration that FL graft should exceed the edges of the dural defect especially laterally. It is then wrapped around a semi rigid pattern (Silastic sheet) and secured with several monofilament 5/0 sutures. The "package" is transferred through the endonasal corridor to the defect. The sutures are divided and taken out; the fascia is unfolded, and its edges are inserted into the subdural space without any twisting or folding of the flap. Finally, the silicone sheet is withdrawn from the nasal cavity, leaving the FL well-stretched in perfect position. RESULTS: We illustrate this technique in the management of a large anterior skull base chondrosarcoma, which necessitated significant bone and dural resection. CONCLUSIONS: The "Gift wrap" technique offers an alternative approach for positioning the FL, which is less time-consuming compared to the traditional technique. Moreover, it enables improved placement of the FL, enhancing its efficacy.

Side-door temporoparietal fascia flap: First experience with a novel technique for anterior skull base reconstruction.

BACKGROUND: Modern achievements in transnasal endoscopic skull base (SB) surgery have led to complex resections that render reconstruction a challenge. Temporoparietal fascia flap (TPFF) is a suitable option for SB reconstruction. The side-door TPFF technique for anterior SB reconstruction is described here for the first time in a real-life surgical setting. METHODS: Patients affected by a SB malignancy who underwent cranioendoscopic resection were included. For reconstruction, a multilayer reconstruction technique including side-door TPFF transposition was employed. RESULTS: TPFF transposition was performed in five patients. The TPFF could be easily transposed via a side-door approach. It adequately covered the edges of the defect and supported optimal healing of the surgical site. During follow-up, vitality and integration of the TPFF were assessed endoscopically and radiologically. CONCLUSIONS: The TPFF side-door transposition technique is a valuable option in anterior SB reconstruction that can provide fast and effective healing, especially in patients needing adjuvant radiotherapy.

The oculomotor cistern and pituitary adenomas: anatomical and clinical study.

OBJECTIVE: The oculomotor cistern (OMC) is a meningeal cuff filled with CSF that contains the oculomotor nerve (cranial nerve [CN] III) at the level of the lateral wall of the cavernous sinus. Only a few studies have investigated the involvement of the OMC by pituitary adenomas (pituitary neuroendocrine tumors [PitNETs]), mainly with relatively small case series. The aim of this study was to perform a histomorphological description of the OMC and systematically analyze its involvement by PitNETs from radiological, clinical, and surgical perspectives. METHODS: Ten hemisellae from formalin-fixed specimens were studied with 3-µm sections. Digital image analysis software was used for morphological and quantitative assessments. Clinical, radiological, surgical, and histological data of patients undergoing endoscopic transsphenoidal surgery for PitNETs at the University of Brescia, Italy, between 2014 and 2021 were recorded. OMC involvement was graded as not compressed, compressed, and invaded. The same surgical team operated on all patients. RESULTS: The OMC had an elliptical shape with an average area of 3.1 mm2 and a length of 5.5 mm. No cisternal points of weakness were recognized in the histomorphological study. Of 315 patients, 246 had complete data: apoplexy and CN III palsy were documented in 6.9% and 8.5%, respectively. OMC compression and invasion were recorded in 106 (43.1%) and 23 (9.3%) patients. Significant associations between OMC involvement and PitNET dimensions (p < 0.001), Knosp grade (p < 0.001), preoperative oculomotor palsy (p < 0.001), Ki-67 percentage (p = 0.009), and recurrence/progression of residual tumor (p = 0.008) were found. A new postoperative CN III palsy was evident in 2%: transient in 4 cases, and persistent in 1 patient treated for a recurrent PitNET who experienced a local infection complication. Preoperative CN III palsy improved in 10 cases. CONCLUSIONS: Significant OMC involvement by PitNETs might be underrecognized, but it can be treated using the endoscopic transsphenoidal approach, and it affects patient outcomes.