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.

Clipping Versus Coiling for Ruptured MCA Aneurysms Associated with Intracerebral Hematoma Requiring Surgical Evacuation.

BACKGROUND: Ruptured middle cerebral artery aneurysm (MCAa) can lead to intracerebral hematoma, and surgical evacuation can be performed in these cases. MCAa can be treated by clipping or before by endovascular therapy (EVT). Our objective was to compare the impact on the functional outcome of MCAa in patients with intracerebral hematoma requiring evacuation. METHODS: This is a multicenter, retrospective, cohort study with nine French neurosurgical units from January 1, 2013, to December 31, 2020. All participants were adult patients who required evacuation of an intracerebral hematoma. We looked for risk factors for poor outcomes by comparing the baseline characteristics and treatments performed by using the 6-month modified Rankin scale score. Poor outcomes were defined by an modified Rankin scale score of 3-6. RESULTS: A total of 162 patients were included. A total of 129 (79.6%) patients were treated by microsurgery, and 33 (20.4%) patients were treated by EVT. In multivariate analysis, factors associated with poor outcomes included hematoma volume, realization of a decompressive craniectomy, occurrence of procedure-related symptomatic cerebral ischemia, occurrence of delayed cerebral ischemia, and EVT. In the propensity score matching analysis (n = 33 per group), poor outcomes were observed in 30% of the patients in the clipping group versus 76% in the EVT group (P < 0.001). These differences may have been related to a longer delay between hospital admission and hematoma evacuation in the EVT group. CONCLUSIONS: In the specific subgroup of ruptured MCAa with intracerebral hematoma that requires surgical evacuation, clipping with concomitant hematoma evacuation could provide better functional outcomes than EVT followed by surgical evacuation.

Lariboisiere Hospital pre-operative surgical checklist to improve safety during transpetrosal approaches.

BACKGROUND: Transpetrosal approaches are technically complex and require a complete understanding of surgical and radiological anatomy. A careful evaluation of pre-operative magnetic resonance imaging and computed tomography scan is mandatory, because anatomical or pathological variations are common and may increase the risk of complications related with the approach. METHODS: Pre-operative characteristics of venous and petrous bone anatomy were analysed and correlated with intraoperative findings, using injected magnetic resonance imaging and thin-slices computed tomography scan. These data regularly checked before each transpetrosal approach were progressively included in the presented checklist. RESULTS: Transpetrosal approaches have been used in 101 patients. Items included in the checklist were petrous bone pneumatization, angle between petrous apex and clivus, dehiscence of petrous carotid artery, dehiscence of geniculate ganglion, distance between superior semicircular canal and middle fossa floor, distance between cochlea and middle fossa floor, sigmoid sinus dominance, transverse sigmoid sinus junction depth to the outer cortical bone, jugular bulb height (high or low), location of the vein of Labbé, characteristics of superior petrosal vein complex. CONCLUSION: The presented checklist provides a systematic scheme of consultation of characteristic of venous and petrous bone anatomy for transpetrosal approaches. In our experience, the use of this checklist reduces the risk of complications related with approach, by minimizing the neglect of crucial information.

A new simple and free tubular device for microscopic transcortical approach to deep-seated lesions: technical note and case example.

BACKGROUND: Surgery for deep-seated brain tumors remains challenging. Transcortical approaches often require brain retraction to ensure an adequate surgical corridor, thus possibly leading to brain damage. Various techniques have been developed to minimize brain retraction such as self-retaining retractors, endoscopic approaches, or tubular retractor systems. Even if they evenly distribute the mechanical pressure over the parenchyma, rigid retractors can also cause some degree of brain damage and have significant disadvantages. We propose here a soft cottonoid retractor for microscopic resection of deep-seated and ventricular lesions. METHODS: Through a small corticectomy, a channel route with a blunt cannula is developed until the lesion is reached. Then, a "balloon-like system" made with a surgical glove is progressively inflated, dilatating the surgical corridor. A mini-tubular device, handmade by suturing a surgical cottonoid, is positioned into the corridor, unfolded, and sutured to the edge of the dura, to prevent it from being progressively expelled from the working channel. This allows a good visualization of the lesion and surrounding structures under the microscope. RESULTS: Advantages of this technique are the softness of the tube walls, the absence of rigid arm to hold the tube, and the possibility for the tube to follow the movements of the instruments and to modify its orientation according to the working area. CONCLUSION: This simple and inexpensive tubular working channel for microscopic transcortical approach is a valuable alternative technique to traditional self-retaining retractor and rigid tube for the microsurgical resection of deep-seated brain tumors.

Atypical evolution of meningiomatosis after discontinuation of cyproterone acetate: clinical cases and histomolecular characterization.

PURPOSE: The long-term use of cyproterone acetate (CPA) is associated with an increased risk of developing intracranial meningiomas. CPA discontinuation most often induces a stabilization or regression of the tumor. The underlying biological mechanisms as well as the reasons why some meningiomas still grow after CPA discontinuation remain unknown. We reported a series of patients presenting CPA-induced meningiomatosis with opposed tumor evolutions following CPA discontinuation, highlighting the underlying histological and genetic features. METHODS: Patients presenting several meningiomas with opposite tumor evolution (coexistence of growing and shrinking tumors) following CPA discontinuation were identified. Clinical and radiological data were reviewed. A retrospective volumetric analysis of the meningiomas was performed. All the growing meningiomas were operated. Each operated tumor was characterized by histological and genetic analyses. RESULTS: Four women with multiple meningiomas and opposite tumor volume evolutions after CPA discontinuation were identified. Histopathological analysis characterized the convexity and tentorial tumors which continued to grow after CPA discontinuation as fibroblastic meningiomas. The decreasing skull base tumor was characterized as a fibroblastic meningioma with increased fibrosis and a widespread collagen formation. The two growing skull base meningiomas were identified as meningothelial and transitional meningiomas. The molecular characterization found two NF2 mutations among the growing meningiomas and a PIK3CA mutation in the skull base tumor which decreased. CONCLUSION: To our knowledge, this is the first report describing an atypical tumor evolution of CPA-associated meningiomas after CPA discontinuation. The underlying biological mechanisms explaining this observation and especially the close relationship between mutational landscapes and embryologic origins of the meninges in CPA-related meningiomas as well as their clonal origin require further research.

Chiasmapexy for secondary empty sella syndrome: diagnostic and therapeutic considerations.

PURPOSE: Secondary empty sella syndrome (SESS) following pituitary surgery remains a diagnostic and therapeutic challenge. The aim of this study was to specify the diagnostic criteria, surgical indications and results of chiasmapexy in the SESS. METHODS: Three cases from two experienced neurosurgical centers were collected and the available literature was reviewed. RESULTS: The 3 patients were operated for a giant non-functioning pituitary adenoma, a cystic macroprolactinoma, and an arachnoid cyst respectively. Postoperative visual outcome was initially improved, and then worsened progressively. At the time of SESS diagnosis, visual field defect was severe in all cases with optic nerve (ON) atrophy in 2 cases. Patients were operated via an endoscopic endonasal extradural approach. One patient was re-operated because of early fat reabsorption. Visual outcome improved in 1 case and stabilized in 2 cases. Statistical analyses performed on 24 cases from the literature review highlighted that patient age and severity of the preoperative visual defect were respectively significant and nearly significant prognostic factors for visual outcome, unlike the surgical technique. CONCLUSION: T2-weighted or CISS/FIESTA sequence MRI is mandatory to visualize adhesions, ON kinking and neurovascular conflict. TS approach is the most commonly used approach. The literature review could not conclude on the need for an intra or extradural approach suggesting case by case adapted strategy. Intrasellar packing with non-absorbable material such as bone should be considered. Severity of the visual loss clearly decreases the visual outcome suggesting early chiasmapexy. In case of severe and long standing symptoms before surgery, benefits and surgical risks should be carefully balanced.

The sellar barrier on preoperative imaging predicts intraoperative cerebrospinal fluid leak: a prospective multicenter cohort study.

BACKGROUND: The type of sellar barrier observed between a pituitary tumor and cerebrospinal fluid (CSF) on preoperative magnetic resonance imaging (MRI) may predict intraoperative CSF leak during endonasal pituitary surgery. This is the first multicentric prospective cohort trial to study the sellar barrier concept and CSF leak rate during endoscopic pituitary surgery. METHODS: This multi-center, international study enrolled patients operated for pituitary adenomas via fully endoscopic endonasal surgery over a period of 4 months. The independent variable was the subtype of sellar barrier observed on preoperative MRI (strong, mixed or weak); the dependent variable was the presence of an intraoperative CSF leak. The primary goal was to determine the association between a particular type of sellar barrier and the risk of intraoperative CSF leak. Appropriate statistical methods were then applied for data analysis. RESULTS: Over the study period, 310 patients underwent endoscopic endonasal surgery for pituitary tumor. Preoperative imaging revealed a weak sellar barrier in 73 (23.55%), a mixed sellar barrier in 75 (24.19%), and a strong sellar barrier in 162 (52.26%) patients. The overall rate of intraoperative CSF leak among all patients was 69 (22.26%). A strong sellar-type barrier was associated with significantly reduced rate of intraoperative CSF leak (RR = 0.08; 95% CI 0.03-0.19; p < 0.0001), while a weak sellar barrier associated with higher rates of CSF leak (RR = 8.54; 95% CI 5.4-13.5; p < 0.0001). CONCLUSIONS: The preoperative MRI of pituitary patients can suggest intraoperative CSF leak rates, utilizing the concept of the sellar barrier. Patients with a weak sellar barrier carry a higher risk for an intraoperative CSF leak, whereas a strong sellar barrier on MRI seems to mitigate intraoperative CSF leak. We propose that preoperatively assessment of the sellar barrier can prepare surgeons for intraoperative CSF leak repair.

Endoscopic endonasal approach to the mesial temporal lobe: anatomical study and clinical considerations for a selective amygdalohippocampectomy.

BACKGROUND: Selective amygdalohippocampectomy (AH) is a surgical option for patients with medically intractable seizures from mesial temporal lobe pathology. The transcranial route is considered the best method to achieve this goal. However, the standard approach through the neocortex is still invasive. The risks can be minimized if the mesial temporal lobe is resected while preserving the lateral temporal lobe and the Meyer's loop. This study explores the feasibility of selective AH by endoscopic endonasal approach (EEA) in cadaveric specimens. METHODS: The endoscopic anatomy of the mesial temporal lobe and the feasibility of a successful selective AH were studied in six hemispheres from three injected human cadavers. Quantitative analyses on the extent of resection and angles of exposure were performed based on CT and MRI studies of pre- and post-selective AH and measurements taken during dissections. RESULTS: The EEA V1-V2 corridor provided a direct and logical line of access to the mesial temporal lobe, following its natural trajectory with no brain retraction and minimal exposure of the pterygopalatine fossa. The components of the mesial temporal lobe were resected just as selectively and easily as the transcranial route, but without compromising the structures of the lateral temporal lobe or the Meyer's loop. CONCLUSIONS: The EEA V1-V2 corridor demonstrated its selective resectability and accessibility of the mesial temporal lobe in cadaveric specimens. The clinical value of this approach should be explored responsibly by a surgeon with both competent microsurgical skills and experiences in EEA.

Hybrid antero-lateral transcondylar approach to the clivus: a laboratory investigation and case illustration.

BACKGROUND: Surgical treatment of lesions involving the ventral craniovertebral junction (CVJ) and the lower clivus, traditionally involved complex lateral or transoral approaches to the skull base. However, mid or upper clivus involvement requires more extensive lateral approaches. Recently, the endoscopic endonasal approach (EEA) has become the standard for upper CVJ lesions and medial clival, and a valuable alternative for those tumors extending in its upper third as well as laterally. However, the EEA is associated with an increased risk of post-operative CSF leakage and infection when the tumor is characterized by an intradural extension. Furthermore, whenever the tumor has significant lateral and/or inferior extension below the odontoid process, the chances for a complete resection decrease. METHOD: To analyze the extent of exposure of a hybrid microscopic-endoscopic transcondylar antero-lateral approach to the CVJ and clival region, and to verify its effectiveness in terms of mid and upper clival access. Five silicone-injected cadaver heads were used. Following a standard antero-lateral approach, condylectomy and jugular tubercle drilling were performed, after which angled endoscopes were utilized to extend the bone resection to the clivus. A volumetric assessment of the amount of clival removal was carried out. A case of CVJ chordoma operated through this approach is presented. RESULTS: The hybrid antero-lateral transcondylar approach provides adequate exposure of the ventral CVJ, up to the dorsum sellae and the sphenoid sinus, the contralateral petrous apex, and the contralateral paraclival internal carotid artery (ICA). Approximately 60% of the total clival volume can be removed with this approach. The main limitation is the limited visualization of the ipsilateral paraclival ICA and petrous apex. CONCLUSION: The hybrid antero-lateral transcondylar approach is a valuable surgical option for CVJ tumor extending from C2 to the mid and upper clivus.

Clinical, pathologic, and imaging characteristics of pituitary null cell adenomas as defined according to the 2017 World Health Organization criteria: a case series from two pituitary centers.

PURPOSE: The 2017 World Health Organization classification of pituitary tumors redefined pituitary null cell adenomas (NCAs) by restricting this diagnostic category to pituitary tumors that are negative for pituitary transcription factors and adenohypophyseal hormones. The clinical behavior of this redefined entity has not been widely studied, and this is a major shortcoming of the classification. This study evaluated the imaging and clinical features of NCAs from two pituitary centers and compared them with those of gonadotroph adenomas (GAs). METHODS: Imaging, pathologic, and clinical characteristics of NCAs and GAs were retrospectively reviewed. Tumor immunohistochemistry was performed to confirm absence of adenohypophyseal hormones and pituitary transcription factor expression. RESULTS: Thirty-one NCAs were compared with 38 GAs. NCAs were more likely to invade the cavernous sinus (15/31 [48%] vs. 5/38 [13%], P = .003) and had a higher proliferative index (i.e., MIB-1 > 3%, 11/31 [35%] vs. 5/38 [13%], P = .04). Gross total resection was less likely in the NCA group (19/31 [61%] vs. 33/38 [87], P = .02). Progression-free survival was worse in the NCA cohort (5-year progression-free survival, 0.70 vs. 1.00; P = .011, by log-rank test). CONCLUSIONS: Compared with GAs, NCAs are more invasive at the time of presentation and have a more aggressive clinical course. This study provides evidence that NCAs represent a distinct clinicopathologic entity with behavior that differs adversely from that of GAs. This may inform clinical decision-making, including frequency of postoperative tumor surveillance and timing of adjunctive treatments.

Spontaneous regression of meningiomas after interruption of nomegestrol acetate: a series of three patients.

BACKGROUND: The relationship between increased meningioma incidence and growth and long-term hormonal therapy with cyproterone acetate (CPA) in women has been recently established in literature. Following the raise in awareness from hormonal treatment, we describe a potential relationship between the progesterone agonist nomegestrol acetate (NOMAC) and meningioma growth. METHODS: After implementation of a screening protocol to detect potential interactions between hormonal exposure and occurrence of meningioma, we identified patients taking NOMAC and newly diagnosed with a meningioma. NOMAC was stopped and those patients were followed tightly both clinically and radiologically. Retrospective volumetric analysis of the tumors was performed on the imaging. RESULTS: Three patients were identified for the study. After cessation of the NOMAC, tumor shrinkage was documented for all meningiomas within the first month. Up to 70% of tumor volume reduction was observed during the first year of follow-up in one of them. None of the patients developed new symptoms. CONCLUSION: We report the first cases of meningiomas responsiveness to discontinuation of hormonal therapy with NOMAC. Similarly to cases associated with long-term CPA intake, tumor reduction, and improvement of clinical symptoms can be observed after cessation of NOMAC.

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.

Growth stabilization and regression of meningiomas after discontinuation of cyproterone acetate: a case series of 12 patients.

BACKGROUND: The relationship between meningiomas and exogenous sex hormones is well known, but cyproterone acetate (CA), a progesterone agonist, seems to have a stronger influence on tumor growth. OBJECTIVE: To show the close relationship between CA treatment and meningioma growth. METHODS: Since 2010, all patients referred to our clinic for a suspicion of meningioma were questioned specifically about exogenous sex hormone intake and more specifically about CA intake. Twelve patients harboring one or multiple meningiomas and treated with CA were identified. CA was stopped in all cases. Tumor volumes and diameters were measured on serial MRIs and compared to the last MRI before CA withdrawal. RESULTS: Ten patients with multiple tumors had been taking the drug for a longer period of time (mean of 20.4 years) than the two patients with one tumor (10 years). Two patients with multiple tumors underwent surgery because of rapidly decreased visual acuity at the time of diagnosis. Discontinuation of CA led to tumor shrinkage in 11 patients and a stop in tumor growth in one [mean tumor volume reduction was around 10 cm(3)/year; range (0.00; 76)]. There was no regrowth during a mean follow-up period of 12 months (range: 5-35). CONCLUSION: For patients diagnosed with a meningioma and treated with CA, medication withdrawal followed by observation should be the first line of treatment. Care should be taken with long-term use of high doses of CA, and serial brain MRIs should be considered after several years of CA.

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.

Embolization of the middle meningeal artery for the prevention of chronic subdural hematoma recurrence in high-risk patients: a randomized controlled trial-the EMPROTECT study protocol.

BACKGROUND: Middle meningeal artery (MMA) embolization has been proposed as a treatment of chronic subdural hematoma (CSDH). The benefit of the procedure has yet to be demonstrated in a randomized controlled trial. We aim to assess the efficacy of MMA embolization in reducing the risk of CSDH recurrence 6 months after burr-hole surgery compared with standard medical treatment in patients at high risk of postoperative recurrence. METHODS: The EMPROTECT trial is a multicenter open label randomized controlled trial (RCT) involving 12 French centers. Adult patients (≥18 years) operated for CSDH recurrence or for a first episode with a predefined recurrence risk factor are randomized 1:1 to receive either MMA embolization within 7 days of the burr-hole surgery (experimental group) or standard medical care (control group). The number of patients to be included is 342. RESULTS: The primary outcome is the rate of CSDH recurrence at 6 months. Secondary outcomes include the rate of repeated surgery for a homolateral CSDH recurrence during the 6-month follow-up period, the rate of disability and dependency at 1 and 6 months, defined by a modified Rankin Scale (mRS) score ≥4, mortality at 1 and 6 months, total cumulative duration of hospital stay during the 6-month follow-up period, directly or indirectly related to the CSDH and embolization procedure-related complication rates. CONCLUSIONS: The EMPROTECT trial is the first RCT evaluating the benefit of MMA embolization as a surgical adjunct for the prevention of CSDH recurrence. If positive, this trial will have a significant impact on patient care. TRIAL REGISTRATION NUMBER: NCT04372147.

Pachymeningitis associated with IgG4-related disease and ANCA positivity: Case report and review of the literature.

OBJECTIVE: Hypertrophic pachymeningitis is a rare clinical disorder involving localized or diffuse thickening of the dura mater. Considering pachymeningitis is both in the clinical spectrum of IgG4-RD and ANCA vasculitis (specifically granulomatosis with polyangiitis), an overlap syndrome is discussed. METHODS: We report a case of hypertrophic pachymeningitis revealed by headache and cranial nerve dysfunction, and coexistence of biopsy-proven IgG4-RD pachymeningitis and MPO-ANCA positivity. Furthermore, all cases previously reported in the literature of pachymeningitis with IgG4-RD and presence of ANCA were analyzed. RESULTS: Thirteen patients with pachymeningitis, IgG4-RD and ANCA were analyzed. Patients with HP-related IgG4 and ANCA are mainly male (8, 62%). Median age at diagnosis was 64 years. Main clinical manifestations at diagnosis were localized to the head and neck with headaches (10, 77%), cranial nerve dysfunction (7, 54%), hearing impairment (6, 46%) and vertigo (4, 31%). Except 1 patient with diffuse aortitis, no other systemic manifestation was observed at diagnosis and during follow-up. Serum IgG4 was often elevated (11, 85%) and ANCA was mainly with myeloperoxidase specificity (11, 85%). Seven patients had cerebrospinal fluid analyse with lymphocytic pleocytosis in 5 cases (71%), elevated proteins in 4 cases (57%), positive oligoclonal bands in 3 cases (42%) and decreased glucose in one case (14%). On the MRI, the thickening of the dura mater concerned most often the posterior fossa, in 7 cases (54%). Among 10 cases with histological findings, all showed increased IgG4-positivity of plasma cells, 50% lymphocytic infiltrate but none presented the three major histological criteria of IgG4-related disease. Three (30%) showed histological signs of vasculitis with vascular wall damage and/or giant cells. Among the 12 patients treated with steroid therapy, a clinical improvement was noted in 11 cases (92%). Relapse occurred during tapering in 4 patients (33%). An immunosuppressive drug was added in 2nd line for 7 cases (54%), with a clinical improvement in all. CONCLUSION: Pachymeningitis with IgG4 and ANCA seems a localized disease to the head and neck. Leptomeningeal biopsy commonly found IgG4 criteria and no vasculitis. All patients responded well to steroid therapy and immunosuppressive drugs, especially rituximab, with clinical and radiological improvement but relapse and/or sequelae are not uncommon.

Computed tomography angiography for quantification of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

PURPOSE: The purpose of this study was to assess the accuracy of computed tomography angiography (CTA) for quantification of cerebral vasospasm following aneurysmal subarachnoid hemorrhage in proximal and middle segments of intracranial arteries. MATERIALS AND METHODS: Twenty consecutive patients (7 men, 13 women; mean age, 47 ± 7 [SD] years; age range: 27-78 years) with aneurysmal subarachnoid hemorrhage who underwent CTA and digital subtracted angiography (DSA) with a 6-hour window at baseline and during vasospasm period were included. Twelve artery segments were analyzed in each patient. Vasospasm was blindly quantified on CTA and digital subtracted angiography (DSA) by two independent readers with discordance > 10% resolved by open data consensus. Inter-reader and inter-test correlations with DSA as reference, and causes of discordant readings were analyzed. The best sensitivity and specificity of CTA for determination of vasospasm ≥ 50% on DSA was determined using receiver operating curve analysis. RESULTS: Two-hundred-and-ten arterial segments were analyzed after exclusion of 30 segments with missing data or metallic artifacts. An inter-reader discordance >10% was observed in 82 segments (82/210; 39% [95% CI: 32-46]). Inter-test discordances >10% were observed respectively in 115 segments (115/210; 55% [95% CI: 49-62]) with the junior reader and in 73 segments (73/210; 35% [95% CI: 29-42]) with the senior reader. They were related to reader error in 55 (55/210; 26% [95% CI: 20-32]) with the junior reader and 13 (13/210; 6% [95% CI: 3-9]) with the senior reader, as well systematic biases in 8 (8/210; 4% [95% CI: 1-6]), and intrinsic limitation in 52 (52/210; 25% [95% CI: 19-31]). Best sensitivity and specificity of CTA were observed for a threshold value of 30% (sensitivity = 88% [95% CI: 78-97%]; specificity = 84% [95% CI: 77-90%]; area under curve = 0.92 [95% CI: 0.86-0.97]). On a patient basis, sensitivity was 100% (specificity = 60% [95% CI: 38-81%]; area under curve = 0.97 [95% CI: 89-100%] for this same threshold. CONCLUSION: Our study shows a moderate accuracy of CTA for the quantification of cerebral vasospasm, mostly related to challenging interpretation and intrinsic limitations. CTA may rule-out angiographic vasospasm ≥ 50% when no segment has vasospasm over than 30%.

DNA methylation-based prognostic subtypes of chordoma tumors in tissue and plasma.

BACKGROUND: Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes. METHODS: Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available. RESULTS: Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1-94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poor-performing "Immune-infiltrated" subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing "Cellular" subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versus-other binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52-1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data. CONCLUSIONS: Here, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome-based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.

Intracranial venous sinus stenting for the treatment of lateral sinus stenoses: An analysis of 200 patients.

PURPOSE: The purpose of this study was to analyze the long-term efficacy and safety of intracranial venous sinus stenting in a large cohort of patients with any type of presentation of primary lateral venous sinus stenosis (VSS). MATERIALS AND METHODS: A retrospective cohort study was performed including patients treated by venous sinus stenting for symptomatic VSS from 2012 to 2019. Successful primary resolution of symptoms without adjunctive treatment or recurrence, and complications after stenting were analyzed at the last follow-up time point. RESULTS: Two-hundred patients were included. There were 14 men and 186 women with a mean age of 39±14 (SD) years (age range: 13-75 years). Presenting symptoms included venous pulsatile tinnitus in 168 patients (168/200; 84%), idiopathic intracranial hypertension in 100 patients (100/200; 50%) and/or spontaneous cerebrospinal fluid leak in 35 patients (35/200; 17%). The overall rate of successful primary resolution of any typical presenting symptoms was 79% (95% CI: 73-85%). This rate ranged from 74% to 93% depending on the symptom with no significant difference between patients with and those without idiopathic intracranial hypertension (P=0.08). Recurrence rate was 10% (95% CI: 6-14%). No death or permanent morbidity were observed during a median follow-up of 2.2 years (Q1, Q3: 1.4, 3.3; range: 1-7.7 years). CONCLUSION: Our study shows that venous sinus stenting has a low morbidity and high success rate at long-term follow-up for the treatment of idiopathic intracranial hypertension, venous pulsatile tinnitus or spontaneous cerebrospinal fluid leak associated with VSS. The excellent safety suggests considering this treatment as first-line treatment when medical management is ineffective or poorly tolerated.