Screening for intracranial aneurysms in autosomal dominant polycystic kidney disease is cost-effective.

Intracranial aneurysm rupture is a dramatic complication of autosomal dominant polycystic kidney disease (ADPKD). It remains uncertain whether screening should be widespread or only target patients with risk factors (personal or familial history of intracranial aneurysm), with an at-risk profession, or those who request screening. We evaluated this in a single-center cohort of 495 consecutive patients with ADPKD submitted to targeted intracranial aneurysm screening. Cerebral magnetic resonance angiography was proposed to 110 patients with a familial history of intracranial aneurysm (group 1), whereas it was not our intention to propose it to 385 patients without familial risk (group 2). Magnetic resonance angiography results, intracranial aneurysm prophylactic repair, rupture events, and cost-effectiveness of intracranial aneurysm screening strategies were retrospectively analyzed. During a median follow up of 5.9 years, five non-fatal intracranial aneurysm ruptures occurred (incidence rate 2.0 (0.87-4.6)/1000 patients-year). In group 1, 90% of patients were screened and an intracranial aneurysm was detected in 14, treated preventively in five, and ruptured in one patient despite surveillance. In group 2, 21% of patients were screened and an intracranial aneurysm was detected in five, and treated preventively in one. Intracranial aneurysm rupture occurred in four patients in group 2. Systematic screening was deemed cost-effective and provides a gain of 0.68 quality-adjusted life years compared to targeted screening. Thus, the intracranial aneurysm rupture rate is high in ADPKD despite targeted screening, and involves mostly patients without familial risk factors. Hence, cost-utility analysis suggests that intracranial aneurysm screening could be proposed to all ADPKD patients.

Circumferential Thick Enhancement at Vessel Wall MRI Has High Specificity for Intracranial Aneurysm Instability.

Purpose To identify wall enhancement patterns on vessel wall MRI that discriminate between stable and unstable unruptured intracranial aneurysm (UIA). Materials and Methods Patients were included from November 2012 through January 2016. Vessel wall MR images were acquired at 3 T in patients with stable (incidental and nonchanging over 6 months) or unstable (symptomatic or changing over 6 months) UIA. Each aneurysm was evaluated by using a four-grade classification of enhancement: 0, none; 1, focal; 2, thin circumferential; and 3, thick (>1 mm) circumferential. Inter- and intrareader agreement for the presence and the grade of enhancement were assessed by using κ statistics and 95% confidence interval (CI). The sensitivity, specificity, and negative and positive predictive values of each enhancement grade for differentiating stable from unstable aneurysms was compared. Results The study included 263 patients with 333 aneurysms. Inter- and intrareader agreement was excellent for both the presence of enhancement (κ values, 0.82 [95% CI: 0.67, 0.99] and 0.87 [95% CI: 0.7, 1.0], respectively) and enhancement grade (κ = 0.92 [95% CI: 0.87, 0.95]). In unruptured aneurysms (n = 307), grade 3 enhancement exhibited the highest specificity (84.4%; 233 of 276; 95% CI: 80.1%, 88.7%; P = .02) and negative predictive value (94.3%; 233 of 247) for differentiating between stable and unstable lesions. There was a significant association between grade 3 enhancement and aneurysm instability (P < .0001). Conclusion In patients with intracranial aneurysm, a thick (>1 mm) circumferential pattern of wall enhancement demonstrated the highest specificity for differentiating between stable and unstable aneurysms. © RSNA, 2018.

Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas.

BACKGROUND: The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas. METHODS: Eighty-three consecutive adult patients (50 men; mean age 60 years) with newly diagnosed supratentorial primary glioblastomas that underwent surgical resection with intraoperative carmustine wafers implantation (n = 7.1 ± 1.7) were retrospectively studied. RESULTS: The median overall survival (OS) was 15.8 months with 56 patients dying over the course of the study. There was no significant association between the number of implanted carmustine wafers and complication rates (four surgical site infections, one death). The OS was significantly longer in Stupp regimen patients (19.5 months) as compared with patients with other postoperative treatments (13 months; p = 0.002). In addition patients with eight or more implanted carmustine wafers survived longer (24.5 months) than patients with seven or less implanted wafers (13 months; p = 0.021). Finally, regardless of the number of carmustine wafers, median OS was significantly longer in patients with a subtotal or total resection (21.5 months) than in patients with a partial resection (13 months; p = 0.011). CONCLUSIONS: The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas. The prognostic value of this treatment association should be evaluated in a multicenter trial, ideally in a randomized and placebo-controlled one.

Does aneurysmal wall enhancement on vessel wall MRI help to distinguish stable from unstable intracranial aneurysms?

BACKGROUND AND PURPOSE: Arterial wall enhancement on vessel wall MRI was described in intracranial inflammatory arterial disease. We hypothesized that circumferential aneurysmal wall enhancement (CAWE) could be an indirect marker of aneurysmal wall inflammation and, therefore, would be more frequent in unstable (ruptured, symptomatic, or undergoing morphological modification) than in stable (incidental and nonevolving) intracranial aneurysms. METHODS: We prospectively performed vessel wall MRI in patients with stable or unstable intracranial aneurysms. Two readers independently had to determine whether a CAWE was present. RESULTS: We included 87 patients harboring 108 aneurysms. Interreader and intrareader agreement for CAWE was excellent (κ=0.85; 95% confidence interval, 0.75-0.95 and κ=0.90; 95% confidence interval, 0.83-0.98, respectively). A CAWE was significantly more frequently seen in unstable than in stable aneurysms (27/31, 87% versus 22/77, 28.5%, respectively; P<0.0001). Multivariate logistic regression, including CAWE, size, location, multiplicity of aneurysms, and daily aspirin intake, revealed that CAWE was the only independent factor associated with unstable status (odds ratio, 9.20; 95% confidence interval, 2.92-29.0; P=0.0002). CONCLUSIONS: CAWE was more frequently observed in unstable intracranial aneurysms and may be used as a surrogate of inflammatory activity in the aneurysmal wall.

[Subarachnoid hemorrhage in young patients]. / Hémorragie méningée du sujet jeune.

Subarachnoid hemorrhage (SAH) accounts for 5 % of strokes with a high rate of death and morbidity. It occurs in young patients, often hypertensive and smoking. Patients usually present with sudden headache. Initial clinical evaluation uses a prognosis grading scale including level of consciousness and motor deficit on admission (WFNS scale). Unenhanced CT brain imaging demonstrates the SHA together with evaluation of the initial blood amount, predictive of the occurrence of cerebral vasospasm that may lead to delayed cerebral ischemia. After referral to a multidisciplinary center with neurovascular expertise, MR, CT and/or catheter angiography detects the ruptured aneurysm, the cause of SAH in 85 % of cases. Since rebleeding is an imminent danger, occlusion of the aneurysm should be performed, as soon as possible and within the first 72 heures, either by an endovascular or microsurgical approach. Medical management includes early detection of hydrocephalus and cerebral vasospasm is a devastating complication inducing death and functional impairment. Prevention strategies remain limited and include maintenance of normovolemia and calcium antagonists such as nimodipine. Treatment of cerebral vasospasm associates maintenance of cerebral perfusion and more invasive techniques such as chemical or mechanical angioplasty.

Spinal meningiomas, from biology to management - A literature review.

Meningiomas arise from arachnoidal cap cells of the meninges, constituting the most common type of central nervous system tumors, and are considered benign tumors in most cases. Their incidence increases with age, and they mainly affect females, constituting 25-46% of primary spinal tumors. Spinal meningiomas could be detected incidentally or be unraveled by various neurological symptoms (e.g., back pain, sphincter dysfunction, sensorimotor deficits). The gold standard diagnostic modality for spinal meningiomas is Magnetic resonance imaging (MRI) which permits their classification into four categories based on their radiological appearance. According to the World Health Organization (WHO) classification, the majority of spinal meningiomas are grade 1. Nevertheless, they can be of higher grade (grades 2 and 3) with atypical or malignant histology and a more aggressive course. To date, surgery is the best treatment where the big majority of meningiomas can be cured. Advances in surgical techniques (ultrasonic dissection, microsurgery, intraoperative monitoring) increase the complete resection rate. Operated patients have a satisfactory prognosis, even in those with poor preoperative neurological status. Adjuvant therapy has a growing role in treating spinal meningiomas, mainly in the case of subtotal resection and tumor recurrence. The current paper reviews the fundamental epidemiological and clinical aspects of spinal meningiomas, their histological and genetic characteristics, and their management, including the various surgical novelties and techniques.

Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases.

IMPORTANCE: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. OBJECTIVE: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. DESIGN: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. SETTING: Monocentric, retrospective, real-life cohort of patients with LM from melanoma. PARTICIPANTS: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. EXPOSURE: Impact of new systemic therapies and radiotherapy. RESULTS: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM "confirmed" or "probable" after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09-1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25-6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. CONCLUSION: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

Small vessel disease in patients with subarachnoid hemorrhage: Prevalence and associations with vasospasm occurrence, severity and clinical outcomes.

PURPOSE: Investigating the associations between cerebral small vessel disease (cSVD) burden and cerebral vasospasm (CVS), delayed cerebral ischemia (DCI) and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Consecutive aSAH patients with initial (<7 days after onset) and 3-month follow-up brain magnetic resonance imaging (MRI) and clinical evaluation at 6 months were included. The cSVD burden score was built using MRI criteria. CVS was defined according to transcranial Doppler examination and computed tomography (CT) or digital subtraction angiography. DCI was defined by the appearance of hyperintense fluid-attenuated inversion recovery lesions, with territorial or cortico-subcortical distribution, between initial MRI and 3-month MRI. The modified Rankin scale of ≤2 at 6 months was considered a favorable outcome. Using univariate and multivariable analyses, we investigated the associations between cSVD and CVS, DCI and clinical outcome. RESULTS: A total of 113 patients were included in the study sample (median age 49.1 years (IQR 42.1-60.8), 70/113 females). The burden of cSVD was mild with a median of 0 (IQR 0-1). When comparing patients with no/mild versus those with moderate/severe cSVD burden, we did not find a univariable difference regarding vasospasm occurrence (60% versus 46.1%, p = 0.54), DCI (20.2% versus 23%, p = 0.66) or favorable outcome at 3 months (94% versus 83.3%, p = 0.20). There was a univariable trend towards more frequent favorable outcome in patients with no/milde white matter hyperintensities versus those with moderate/severe white matter hyperintensities (92% versus 85%, p = 0.09). In multivariable models, cSVD markers were not associated with CVS occurrence and severity, DCI or clinical outcome. CONCLUSIONS: In patients with mild aSAH, the burden of cSVD as assessed by MRI is minimal and is not associated with CVS, DCI or clinical outcome.

Radiosurgery with or without A 2-mm margin for 93 single brain metastases.

PURPOSE: Retrospective comparison of Linac radiosurgery (RS) in 93 single brain metastases with or without a 2-mm margin. PATIENTS AND METHODS: A total of 153 patients had Linac RS (between April 1992 and June 2004), with 139 patients (90.8%) evaluable in June 2005. Sixty-one patients (44%) had extracranial lesions and 65 patients had neurologic symptoms (47%). RS alone: 105 patients (66%); RS +whole brain radiotherapy: 34 patients (24%). Single metastasis: 93/139 patients; classic RS: 42/93 patients; 2-mm margin: 51/93 patients; 30 multiple lesions patients were excluded. TREATMENT: 15 Mv X-ray Linac, circular minibeams, 8-30 mm, four to six noncoplanar coronal arcs. Isodose was 60-80%; doses were 10-20 Gy. FOLLOW-UP: 12 months-13 years; median, 14 months. RESULTS: Local control (LC) was not improved in 51 margin patients vs. 42 classic RS patients: 1 year: 69.1% and 72.4%. Two-year LC rate: 64% and 54.7%, respectively. Survival: median classic RS: 11.3 months; margin RS, 19 months (p = 0.34) and 1 year, 41.6% and 60.2%, respectively. Margin RS patients had a significantly higher rate of severe parenchymal complications: 19.6% vs. 7.1% (p = 0.02); surgery was necessary in 4 of 51 cases vs. 1 of 42 classic RS cases. CONCLUSION: No increase of 1- and 2-year LC rate in margin RS or survival and median survival: 11.3 vs. 19 months (NS) 2-mm margin associated with more severe parenchymal complications (p = 0.02). This procedure is therefore not recommended. Late CT images and 1-mm margin as recommended by pathologists, use of three-dimensional magnetic resonance imaging and fuzzy method to calculate volumes may yield better results. Stereotactic hypofractionation requires further studies.

Real-time Brain Tumor imaging with endogenous fluorophores: a diagnosis proof-of-concept study on fresh human samples.

The primary line of therapy for high-grade brain tumor is surgical resection, however, identifying tumor margins in vivo remains a major challenge. Despite the progress in computer-assisted imaging techniques, biopsy analysis remains the standard diagnostic tool when it comes to delineating tumor margins. Our group aims to answer this challenge by exploiting optical imaging of endogenous fluorescence in order to provide a reliable and reproducible diagnosis close to neuropathology. In this study, we first establish the ability of two-photon microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain metastasis using the endogenous fluorescence response of fresh human brain sample. Two-photon fluorescence images were compared to gold standard neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative analysis on spectral and fluorescence lifetime measurements resulted in building a scoring system to discriminate brain tissue samples.

[Screening and management of intracranial aneurisms in patients with autosomal dominant polycystic kidney disease]. / Dépistage et prise en charge des anévrismes intracrâniens chez les patients atteints de polykystose rénale autosomique dominante.

Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease. Intracranial aneurysm prevalence in this population is four to five times higher than the prevalence in the general population. The most frequent complication of intracranial aneurysms is rupture with subarachnoidal hemorrhage, which is associated with a high morbidity and mortality. The only identified risk factor for unruptured intracranial aneurysm is a family history of intracranial aneurysm. However, most cases of aneurysm rupture occur without any family history of intracranial aneurysm. Magnetic resonance angiography without contrast medium injection facilitates screening, and progress have been made in preventive (endovascular or neurosurgical) treatment of intracranial aneurysm. Recommendations have recently been published concerning intracranial aneurysm screening, and suggest screening patients with autosomal dominant polycystic kidney disease and a family history of intracranial aneurysm, those who have an at-risk activity and those who request screening despite adequate information. Conflicting opinions exist, however, in the literature. Furthermore, a study of practice was conducted among French-speaking nephrologists in Europe and showed that approximately a third of the participants were in favor of systematic screening for intracranial aneurysm in all patients with autosomal dominant polycystic kidney disease. Beyond intracranial aneurysm prevalence, it is necessary to better define rupture rates in the autosomal dominant polycystic kidney disease population, with and without familial history of intracranial aneurysm. This would allow optimizing intracranial aneurysm screening practices in autosomal dominant polycystic kidney disease.

Multimodal optical analysis discriminates freshly extracted human sample of gliomas, metastases and meningiomas from their appropriate controls.

Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

Multimodal optical analysis of meningioma and comparison with histopathology.

Meningioma is the most frequent primary central nervous system tumor. The risk of recurrence and the prognosis are correlated with the extent of the resection that ideally encompasses the infiltrated dura mater and, if required, the infiltrated bone. No device can deliver real-time intraoperative histopathological information on the tumor environment to help the neurosurgeon to achieve a gross total removal. This study assessed the abilities of nonlinear microscopy to provide relevant and real-time data to help resection of meningiomas. Nine human meningioma samples (four World Health Organization Grade I, five Grade II) were analyzed using different optical modalities: spectral analysis and imaging, lifetime measurements, fluorescence lifetime imaging microscopy, fluorescence emitted under one- and two-photon excitation and the second-harmonic generation signal imaging using a multimodal setup. Nonlinear microscopy produced images close to histopathology as a gold standard. The second-harmonic generation signal delineated the collagen background and two-photon fluorescence underlined cell cytoplasm. The matching between fluorescence images and Hematoxylin and Eosin staining was possible in all cases. Grade I meningioma emitted less autofluorescence than Grade II meningioma and Grade II meningioma exhibited a distinct lifetime value. Autofluorescence was correlated with the proliferation rates and seemed to explain the observed differences between Grade I and II meningiomas. This preliminary multimodal study focused on human meningioma samples confirms the potential of tissue autofluorescence analysis and nonlinear microscopy in helping intraoperatively neurosurgeons to reach the actual boundaries of the tumor infiltration. Correspondence between H&E staining (top pictures) and the two-photon fluorescence imaging (bottom pictures).

Screening for Unruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Survey of 420 Nephrologists.

BACKGROUND: Despite a high prevalence of intracranial aneurysm (ICA) in autosomal dominant polycystic kidney disease (ADPKD), rupture events are rare. The current recommendations for ICA screening are based on expert opinions and studies with low levels of evidence. OBJECTIVES: The aim of our study was to describe the attitudes of practicing nephrologists in Europe towards screening for ICA using magnetic resonance angiography (MRA). METHODS: We conducted a web-based survey among 1315 European French-speaking nephrologists and nephrology residents. An anonymous, electronic questionnaire including 24 independent questions related to ICA screening modalities, indications and participant profiles was sent by email between September and December 2014. Four hundred and twenty nephrologists (mostly from France) participated, including 31 nephrology residents; the response rate was 32%. RESULTS: Systematic screening for ICA was advocated by 28% of the nephrologists. A family history of ICA rupture, sudden death, stroke and migraine were consensual indications for screening (> 90% of the panel). In other clinical situations largely not covered by the recommendations (pregnancy, nephrectomy, kidney transplantation, cardiac or hepatic surgery, uncontrolled hypertension, lack of familial ADPKD history, at-risk activity, tobacco use), the attitudes towards screening were highly divergent. ICA screening was influenced by nephrologists experience with ADPKD and by their practice setting. The majority of participants (57%) would not repeat a normal ICA screening. Only a few participants (22%) knew that non-contrast MRA was the reference diagnostic tool for ICA screening, whereas most participants thought that contrast enhancement was necessary to screen for ICA. The results from the nephrology residents were analyzed separately and yielded similar results. CONCLUSION: This practice survey revealed that most nephrologists follow the current recommendations for the initial screening of ICAs. However, more than a quarter of the panel was in favor of systematic ICA screening, most nephrologists did not know that contrast medium was not necessary to screen for ICA using MRA, and many areas of uncertainty remain.

Three-dimensional dynamic MR digital subtraction angiography using sensitivity encoding for the evaluation of intracranial arteriovenous malformations: a preliminary study.

BACKGROUND AND PURPOSE: Our aim was to develop 3D dynamic MR digital subtraction angiography with high temporal resolution without sacrificing spatial resolution by using sensitivity encoding for the evaluation of cerebral arteriovenous malformations. METHODS: Nineteen patients with 19 angiographically proven arteriovenous malformations (16 supratentorial and 3 infratentorial) were assessed by conventional catheter angiography and 3D dynamic MR digital subtraction angiography. A 3D contrast-enhanced gradient-echo sequence with sensitivity encoding based on a parallel imaging technique was performed and acquired 20 dynamic images, repeated 18 times every 1.7 seconds. Three-dimensional dynamic MR digital subtraction angiograms were analyzed independently by two radiologists in a blinded fashion with regard to arteriovenous malformation nidus and venous drainage. Conventional catheter angiography was used as reference. RESULTS: All MR imaging examinations were assessable. Interobserver agreement was excellent for the detection of nidus and for the evaluation of nidus size (kappa = 1 and 0.875, respectively) but moderate for the visualization of the venous drainage (kappa = 0.56). All nidi detected on conventional catheter angiography were clearly depicted on 3D dynamic MR digital subtraction angiography. The evaluation of the size of the nidus by both techniques was similar. On 3D dynamic MR angiograms, veins were correctly analyzed in 17 of 19 arteriovenous malformations. CONCLUSION: Our preliminary study demonstrates that 3D dynamic MR digital subtraction angiography using sensitivity encoding with a high spatial resolution is appropriate for the assessment of arteriovenous malformations.

Repeat linear accelerator radiosurgery for cerebral arteriovenous malformations.

PURPOSE: To evaluate repeat radiosurgery (RS2) for cerebral arteriovenous malformations (AVMs) after failure of initial radiosurgery (RS1). METHODS AND MATERIALS: Between 1986 and 2000, 41 patients underwent RS2. Nine patients were not assessable: seven had insufficient follow-up (RS2 in 1999 and 2000) and two had no recent control angiography data. Thus, 32 (78%) of 41 patients were assessed. Most lesions (29 [90%] of 32) were supratentorial: 22 (69%) on the left, 8 (25%) on the right, and 2 on the midline (6%). The patients had Spetzler-Martin Grade 1-5 (median Grade 3). The symptoms before RS1 included hemorrhage in 20 (63%), epilepsy in 10 (31%), progressive neurologic deficits in 2 (6%), and headaches in 6 (19%). Five patients had two or more symptoms. Twenty-two patients (69%) had received other treatment before RS1, including neurosurgery in 3 patients (9%) and one to six embolizations in 19 patients. At RS1, the median largest nidus dimension was 2.7 cm (range 0.8-5). The median volume was 2.7 cm(3) (range 1.2-9.9). The median time from RS1 to RS2 was 52 months (range 12-126). Between RS1 and RS2, 7 (22%) of 32 patients experienced bleeding. The same irradiation technique was used for RS1 and RS2, except for 2 patients who underwent RS2 at another institution. Circular 15-MV X-ray minibeams (range 6-20 mm) and coronal arcs were used. RS1 was monoisocentric in 75% of cases and multiisocentric in 25%. At RS2, the median largest nidus dimension was 3 cm (range 1.4-5). The median volume was 4.2 cm(3) (range 0.8-13.4). RS2 was monocentric in 72% of cases and multiisocentric in 28%. After RS2, the median follow-up was 19.5 months (range 0-79; mean 25.3). RESULTS: After RS2, the obliteration rate was 59.3% (19 of 32). The median time to arteriographic obliteration was 21 months (range 12-96). The survival rate was 97% (31 of 32). Five of the 13 patients with a nonobliterated nidus experienced complications; 3 had bleeding (9%) and 2 without prior neurologic deficits developed partially regressive neurologic deficits. One patient with a previously existing deficit developed an additional new partially regressive neurologic deficit after an episode of bleeding. Thus, 3 (9%) of 32 patients had neurologic complications. Moderate-grade parenchymal changes at MRI increased after RS2 (88.2% vs. 57.7% after RS1; p = 0.10, not significant). However, necrosis-like changes did not significantly increase. After RS1 failure, salvage may be attempted by embolization, neurosurgery, or RS2. RS2 should be considered after the second successive annual angiogram if reduction of the nidus is <25%. CONCLUSION: The results after RS2 are encouraging. A multidisciplinary approach is mandatory to reduce the initial failure rate and to choose the modality and timing of salvage treatment.

Radiosurgery of cerebral arteriovenous malformations in children: a series of 57 cases.

PURPOSE: To evaluate the efficacy and outcome of Linac radiosurgery (RS) as treatment of cerebral arteriovenous malformations (cAVM) in a series of 57 children. METHODS AND MATERIALS: Between 1984 and 2000, we used Linac radiosurgery to treat 792 patients with cAVM. This series included 57 children (7.2%) under the age of 15 years at the time of RS (range = 7-15 years, median = 12 years). We were able to evaluate 49 of the children (86%) by angiography, 21 boys and 28 girls (sex ratio = 0.75). First symptoms were: hemorrhage, 34 patients (69.4%); seizures, 6 patients (12.5%); headache, 6 patients (12.5%); and progressive neurologic deficit, 1 patient (2.1%). Nidus size ranged from 5 to 50 mm (median = 20 mm). Nidus volume ranged from 0.6 to 16 cc (median = 3.5 cc). Patient distribution according to Spetzler-Martin grade was as follows: Grade 1, n = 5 (11%); Grade 2, n = 18 (35%); Grade 3, n = 21 (40%,); Grade 4, n = 5 (14%); and Grade 5, n = 0%. Twenty-seven patients (55.1%) had other treatment before RS: embolization, n = 14 (31.1%); neurosurgery, n = 9 (20.5%); embolization and neurosurgery, n = 3 (6.1%). RS was performed with the system used for adults. Patients were seated in a Betti armchair. Circular 15 MV X-ray minibeams (6 to 20 mm) were delivered in coronal arcs by a GECGR Saturne 43 Linac. Planification and dosimetry were carried out using the Associated Target Methodology and Dosigray TPS dosimetric systems. The dose at the peripheral isodose (50-70%) ranged from 18 to 28 Gy. Median and mean doses were 25 Gy and 23.8 Gy. Mono-isocentric planification was used in 25 patients (53.2%) and multi-isocentric in 24 patients (2 to 5 isocenters). The overall follow-up ranged from 7 to 172 months (mean 40 months, median 34 months). RESULTS: The overall rate of obliteration (OR) was 30/49 (61.2%). Mean time to obliteration was 34 months (range = 7 to 172 months). OR varied according to nidus size and volume: OR was 80% for nidus <15 mm, 67% for nidus between 15 and 25 mm, and 42% for nidus >25 mm (p = 0.058). OR was 100% for nidus <1 cc, 73% for nidus between 1 and 4 cc, and 40% for nidus of 4 to 10 cc (p = 0.019). OR according to patient gender was 84.2% for boys and 40% for girls. OR according to minimum dose (Dmin) was 44% for Dmin < 15 Gy (p = 0.01), 89% for D min from 15 to 20 Gy, and 100% for Dmin > 20 Gy (p = 0.01). OR was 62% in nonembolized AVM and 58% in previously embolized AVM (NS). OR according to the number of isocenters was 68.2%, 55.6%, 80%, 50%, and 0% for 1, 2, 3, 4, and 5 isocenters, respectively. After multivariate analysis, only Dmin closely correlated with OR (beta = 0.462; SE = 0.244, p = 0.057). Of the 6 patients with seizures before RS, 5 (80%) were seizure-free without medication after RS. One patient died of pneumonia. MORBIDITY: Four patients (8.2%) had bleeding after RS at 39, 45, 51, and 59 months. No new neurologic deficit was found during the follow-up period. Twenty-nine patients underwent magnetic resonance imaging. Thirteen patients (44.8%) showed no parenchymal changes. Thirteen patients (44.8%) had Grade 2 changes, that is, T2 hypersignals. Two patients (6.9%) had Grade 3 changes, and 1 patient (3.4%) had Grade 4 "necrosis-like" changes. CONCLUSION: In our experience, Linac RS has proven to be a safe and effective method to treat cerebral AVM in children <15 years, whether used alone or in association with embolization and/or neurosurgery.

Comparison of deep wound infection rates using a synthetic dural substitute (neuro-patch) or pericranium graft for dural closure: a clinical review of 1 year.

OBJECTIVE: The need to repair dural defects has prompted the use of dura mater substitutes. Many synthetic materials have been used for dural closure. Neuro-Patch (B. Braun Médical S.A., Boulogne, France) is a nonabsorbable microporous fleece composed of polyester urethane that has been approved for human use by the European Union since 1995. To the best of our knowledge, no clinical series with Neuro-Patch have been published thus far, particularly with regard to septic complications. The aim of our study was to compare the safety of Neuro-Patch with that of pericranium graft with regard to postoperative wound infections. METHODS: This is a retrospective study of 1 year's experience including all patients who underwent dural plasty with a Neuro-Patch (n = 61) or pericranium graft (n = 63). The follow-up period was at least 12 months after surgery. Before wound infection rates in the two groups were compared, factors suspected of being risks for neurosurgical site infection were evaluated. RESULTS: Patient characteristics (mean age, neurological diagnosis), surgical procedures, prophylactic antibiotics, and risk factors for surgical infections (including duration of surgery, emergency, contaminated operations, and external cerebrospinal fluid drainage) were similar in the Neuro-Patch and pericranium groups. Deep wound infection rates in the Neuro-Patch and pericranium groups were 15 and 5%, respectively (P = 0.06), and cerebrospinal fluid leaks were significantly more frequent in the Neuro-Patch group (13 versus 1.6%, P < 0.05). CONCLUSION: The results of our investigations show that Neuro-Patch raised the risk of wound infection, as do foreign materials implanted in the body. Synthetic dural grafts should be reserved for when autologous grafts are not sufficient or possible. An extensive prospective multicenter randomized trial is needed to confirm our results.

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling.

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.

[Conservative neurosurgery]. / La neurochirurgie "conservatrice".

"Conservative neurosurgery" is an evident concept. Preservation of brain is by all means the goal of neurosurgical operations because there are no possibilities of compensation in case of lesion of brain parenchyma, either complete or partial. However, there is a great variability of functionnally eloquent areas in the brain; so a lesion may induce or not visible neurological deficits as function of the location of the lesion. The goal of this review article is to scan means used in neurosurgery to spare parenchymal brain, which is often called "minimal invasive neurosurgery" with a special interest of recent and current progress of morphological and functional imaging of the brain.