Intracranial aneurysms in pediatric population: a two-center audit.

OBJECTIVE: Intracranial aneurysms (IA) in children are rare, accounting for less than 5% of all IA. Due to their scarcity, the epidemiology is poorly understood and differs from adults in term of clinical presentation, size, location, and origin. Consequently, the treatment strategies are specific and cannot be only based on data from adult series. The aim of our study was to report the characteristics, management, and outcomes of children treated for IA in two university hospitals located in Normandy (France) over the last 17 years and to perform a literature review of this rare pathology. METHODS: This retrospective study included 18 consecutive children (< 18 years old) admitted with cerebral aneurysm treated in two neurosurgery departments in Normandy, from 2001 to 2018. Computerized tomography and cerebral angiography established the diagnosis. Both endovascular and surgical procedures were discussed in all cases. Data focused on clinical condition at admission, characteristics of the IA, choice of the treatment modalities, and complications. The outcome at follow-up is based on Glasgow outcomes scale (GOS) at 1 year. RESULTS: During the study period, 18 children (mean age: 12.6 years; sex ratio male/female: 2.3) were admitted with 21 IA. Aneurysms had a mean size of 13.6 mm with 4 giant aneurysms and were mostly located in the anterior circulation (16/21). Clinical presentations at onset were sudden symptoms related to a subarachnoid hemorrhage in 13 patients, headaches in 4 patients with giant aneurysm, and asymptomatic in one patient. Among the 13 patients with ruptured IA, 6 presented in poor preoperative condition (Hunt and Hess Grade ≥ 4). Treatment modalities consisted in embolization in 9 patients and surgery in 9 patients including 2 by-pass surgeries in fusiform aneurysms. Complications were similar in the two groups, but two cases of recanalization were observed in the endovascular group. At 1 year of follow-up, 14 children were in good condition (GOS Score > 4) and one died. Three children presented associated IA treated by the same technique as initial aneurysm. CONCLUSIONS: Pediatric aneurysm is a different pathology compared with adults, occurring more frequently in male population with a higher proportion of giant aneurysms and aneurysms located in the internal carotid bifurcation. The use of endovascular techniques has progressed in the last years, but surgery was proposed for half of our population.

Decreased number of deaths related to severe traumatic brain injury in intensive care unit during the first lockdown in Normandy: at least one positive side effect of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has led to severe containment measures to protect the population in France. The first lockdown modified daily living and could have led to a decrease in the frequency of severe traumatic brain injury (TBI). In the present study, we compared the frequency and severity of severe TBI before and during the first containment in Normandy. METHODS: We included all patients admitted in the intensive care unit (ICU) for severe TBI in the two tertiary neurosurgical trauma centres of Normandy during the first lockdown. The year before the containment served as control. The primary outcome was the number of patients admitted per week in ICU. We compared the demographic characteristics, TBI mechanisms, CT scan, surgical procedure, and mortality rate. RESULTS: The incidence of admissions for severe TBI in Normandy decreased by 33% during the containment. The aetiology of TBI significantly changed during the containment: there were less traffic road accidents and more TBI related to alcohol consumption. Patients with severe TBI during the containment had a better prognosis according to the impact score (p=0.04). We observed a significant decrease in the rate of short-term mortality related to severe TBI during the period of lockdown (p=0.02). CONCLUSIONS: Containment related to the COVID-19 pandemic has resulted in a modification of the mechanisms of severe TBI in Normandy, which was associated with a decline in the rate of short-term death in intensive unit care.

Early platelet variation during concomitant chemo-radiotherapy predicts adjuvant temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma patients.

PURPOSE: Temozolomide (TMZ) is known to induce thrombocytopenia but no early predictive test has yet been clearly established. The aim of the study was to retrospectively identify and validate a threshold of early platelet variation predicting TMZ-induced thrombocytopenia during the TMZ phase in patients treated according to the Stupp protocol for glioblastoma. METHODS: A training set was used to analyze variations in platelet count occurring from the first week (W1) to week 6 (W6) during radiotherapy. Our aim was to identify the most relevant platelet decrease associated with TMZ-induced thrombocytopenia ≤ 100 G/L at day 28 during the TMZ phase. The performance of the threshold was confirmed in an independent validation set. RESULTS: Overall, 147 patients were included, 85 and 62 in the training and validation sets, respectively. Twenty-seven patients (18%) experienced at least one TMZ-induced thrombocytopenia in the TMZ phase. A platelet decrease at W6 ≥ 35% (∆W6 ≥ 35%) was identified as the best predictive variation with an AUC of 0.83, a sensitivity of 65%, and a specificity of 96%. In the validation set, ∆W6 ≥ 35% platelet variation was identified as an independent marker of TMZ-induced thrombocytopenia during the TMZ phase (OR 15.23 (95% CI 3.5-107.5)) corresponding to sensitivity of 77% (66-87%), specificity of 73% (62-84%), a positive predictive value of 42% (29-54%), and a negative predictive value of 92% (86-99%). CONCLUSION: Platelet decrease at W6 ≥ 35% during the RT-TMZ phase is an early and simple predictive marker of clinically relevant TMZ-induced thrombocytopenia during TMZ maintenance.

Stereotactic brain biopsy: evaluation of robot-assisted procedure in 60 patients.

BACKGROUND: Frameless stereotactic biopsies, particularly robot-assisted procedures are increasing in neurosurgery centers. Results of these procedures should be at least equal to or greater than frame-based reference procedure. Evaluate robot-assisted technology is necessary in particular, when a team has chosen to switch from one to another method. OBJECTIVE: The objective of our prospective work was (i) to evaluate the success rate of contributive robotic-assisted biopsy in 60 patients, to report the morbidity and mortality associated with the procedure and (ii) to compare it with literature data. METHODS: We performed a prospective and descriptive study including 60 consecutive patients having had robotic-assisted stereotactic biopsy at the Rouen University Hospital, France. All patients had presurgical imaging before the procedure included Magnetic Resonance Imaging merged with Computed Tomography scan acquisition. Registration was mostly performed with a touch-free laser (57/60). A control Computed Tomography scan was always realized at day 0 or day 1 after surgery. Data collected were success rate, bleeding, clinical worsening, infection, and mortality. RESULTS: All the biopsies were considered as contributive and lead to the final diagnosis. In 41/60 patients (68%), the lesion was glial. Six in 60 patients (10%) had visible bleeding without clinical worsening related, 5/60 patients (8.5%) showed clinical impairment following surgery, which was permanent in 2 patients, and 1/60 patient presented generalized seizures. We did not report any infection and mortality. CONCLUSION: Robot-assisted frameless surgery is efficient and provides a reasonable alternative to frame-based procedure. The operating time can be reduced, without increasing morbidity and mortality rates.

Spinal meningioma and factors predictive of post-operative deterioration.

PURPOSE: Spinal meningiomas are slow-growing intradural-extramedullary tumors. They are usually associated with good outcomes. However, there are few descriptions of factors predictive of impaired evolution. Our objective was to identify predictive factors of post-operative deterioration as well as outcomes at follow-up. METHODS: Between 2009 and 2016, 87 patients had surgery for spinal meningioma in our referral center. Clinical presentation, management and outcomes were reported during the post-operative period and at 3-month follow-up. Evaluation was based on post-operative neurological deterioration defined as an increase of at least one point in the McCormick score compared to the status at admission. RESULTS: During the study period, post-operative deterioration occurred in 17 patients (19.5%). Risk factors associated with this deterioration were the absence of pre-operative neurological signs (Relative Risk; RR = 2.38, p = 0.04), an anterior location of the meningioma and a grade 2 meningioma on WHO classification score (RR = 6, p ≤ 0.01). At 3-month follow-up, in patients who initially presented with a motor deficit, partial recovery was found in 75%, stability in 20% and a deterioration of their clinical status in 5%. After a mean follow-up of 92.4 ± 51.9 months, the recurrence rate was 8%. CONCLUSIONS: Spinal meningiomas are usually benign tumors whose treatment is based on complete surgical resection. Progress in surgical techniques has resulted in lower morbidity rates and improvement in post-operative recovery. In this study, we observed several factors associated with clinical deterioration. Before surgery, patients should be fully informed of these predictive factors of post-operative deterioration and their association with surgical morbidity.

Post hemorrhagic hydrocephalus and neurodevelopmental outcomes in a context of neonatal intraventricular hemorrhage: an institutional experience in 122 preterm children.

BACKGROUND: Intraventricular hemorrhage (IVH) is a frequent complication in extreme and very preterm births. Despite a high risk of death and impaired neurodevelopment, the precise prognosis of infants with IVH remains unclear. The objective of this study was to evaluate the rate and predictive factors of evolution to post hemorrhagic hydrocephalus (PHH) requiring a shunt, in newborns with IVH and to report their neurodevelopmental outcomes at 2 years of age. METHODS: Among all preterm newborns admitted to the department of neonatalogy at Rouen University Hospital, France between January 2000 and December 2013, 122 had an IVH and were included in the study. Newborns with grade 1 IVH according to the Papile classification were excluded. RESULTS: At 2-year, 18% (n = 22) of our IVH cohort required permanent cerebro spinal fluid (CSF) derivation. High IVH grade, low gestational age at birth and increased head circumference were risk factors for PHH. The rate of death of IVH was 36.9% (n = 45). The rate of cerebral palsy was 55.9% (n = 43) in the 77 surviving patients (49.4%). Risk factors for impaired neurodevelopment were high grade IVH and increased head circumference. CONCLUSION: High IVH grade was strongly correlated with death and neurodevelopmental outcome. The impact of an increased head circumference highlights the need for early management. CSF biomarkers and new medical treatments such as antenatal magnesium sulfate have emerged and could predict and improve the prognosis of these newborns with PHH.

Microsurgery and Endovascular Therapy for Distal Anterior Cerebral Artery Aneurysm: A Multicenter Retrospective Cohort Study.

BACKGROUND: Distal anterior cerebral aneurysm (DACA) represents 4% of intracranial aneurysms. Two treatment modalities are available: microsurgery and endovascular therapy (EVT). OBJECTIVE: To compare the results between microsurgery and EVT in a modern French cohort. METHODS: A multicenter retrospective cohort study of 3 French neurosurgical units was carried out from January 1, 2015, to December 31, 2020. All participants were adult patients who required treatment for a ruptured or unruptured DACA aneurysm. RESULTS: A total of 69 patients were included; 16 patients (23.2%) were treated by microsurgery and 53 (76.8%) were treated by EVT. Thirty-one patients (44.9%) had ruptured aneurysms. The complication rate was low, with 1 death and 1 symptomatic ischemia. There was no difference in complications between microsurgery and EVT (P = 0.22). The number of retreatments was higher in EVT (15% vs. 0%) but not significantly (P = 0.18). CONCLUSIONS: In the specific subgroup of DACA, both treatment modalities are effective in ruptured and unruptured aneurysms, with a low rate of complications. Retreatment may be more frequent in EVT but it does not lead to more complications.

Applicability of the Edinburgh CT Criteria for Lobar Intracerebral Hemorrhage Associated with Cerebral Amyloid Angiopathy.

OBJECTIVE: Based on histopathology, Edinburgh diagnostic criteria were proposed to consider a nontraumatic intracerebral lobar hemorrhage (ICH) as related to cerebral amyloid angiopathy (CAA) using the initial computed tomography (CT) scan and the APOE genetic status. We aimed to externally validate the Edinburgh prediction model, excluding the APOE genotyping and based on the modified Boston criteria on the MRI for CAA diagnosis METHODS: We included patients admitted for spontaneous lobar ICH in the emergency department between 2016 and 2019 who underwent noncontrast CT scan and MRI. According to the MRI, patients were classified into the CAA group or into the non-CAA group in the case of other causes of ICH. Two neuroradiologists, blinded to the final retained diagnosis, rated each radiological feature on initial CT scan described in the Edinburgh study on initial CT scan RESULTS: A total of 102 patients were included, of whom 36 were classified in the CAA group, 46 in the non-CAA causes group and 20 of undetermined cause (excluded from the primary analysis). The Edinburgh prediction model, including finger-like projections and subarachnoid extension showed an area under receiver operating characteristic curves (AUC) of 0.760 (95% confidence interval, CI: 0.660-0.859) for the diagnosis of CAA. The AUC reached 0.808 (95% CI: 0.714-0.901) in a new prediction model integrating a third radiologic variable: the ICH cortical involvement. CONCLUSION: Using the Boston MRI criteria as a final assessment, we provided a new external confirmation of the radiological Edinburgh CT criteria, which are directly applicable in acute settings of spontaneous lobar ICH and further proposed an original 3­set model considering finger-like projections, subarachnoid extension, and cortical involvement that may achieve a high discrimination performance.

Chiari malformation type I surgery in children: French multicenter 10-year cohort.

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.

Precision Neurosurgery: A Path Forward.

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology.

TERT Promoter Alterations in Glioblastoma: A Systematic Review.

Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth. The aim of this systematic review is to provide an overview of the available data concerning TERT alterations and glioblastoma in terms of incidence, physiopathological understanding, and potential therapeutic implications.

Diagnosis and Management of Glioblastoma: A Comprehensive Perspective.

Glioblastoma is the most common malignant brain tumor in adults. The current management relies on surgical resection and adjuvant radiotherapy and chemotherapy. Despite advances in our understanding of glioblastoma onset, we are still faced with an increased incidence, an altered quality of life and a poor prognosis, its relapse and a median overall survival of 15 months. For the past few years, the understanding of glioblastoma physiopathology has experienced an exponential acceleration and yielded significant insights and new treatments perspectives. In this review, through an original R-based literature analysis, we summarize the clinical presentation, current standards of care and outcomes in patients diagnosed with glioblastoma. We also present the recent advances and perspectives regarding pathophysiological bases as well as new therapeutic approaches such as cancer vaccination and personalized treatments.

Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging.

Duchenne muscular dystrophy (DMD) is a common and severe X-linked myopathy, characterized by muscle degeneration due to altered or absent dystrophin. DMD has no effective cure, and the underlying molecular mechanisms remain incompletely understood. The aim of this study is to investigate the metabolic changes in DMD using mass spectrometry-based imaging. Nine human muscle biopsies from DMD patients and nine muscle biopsies from control individuals were subjected to untargeted MSI using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry. Both univariate and pattern recognition techniques have been used for data analysis. This study revealed significant changes in 34 keys metabolites. Seven metabolites were decreased in the Duchenne biopsies compared to control biopsies including adenosine triphosphate, and glycerophosphocholine. The other 27 metabolites were increased in the Duchenne biopsies, including sphingomyelin, phosphatidylcholines, phosphatidic acids and phosphatidylserines. Most of these dysregulated metabolites are tightly related to energy and phospholipid metabolism. This study revealed a deep metabolic remodelling in phospholipids and energy metabolism in DMD. This systems-based approach enabled exploring the metabolism in DMD in an unprecedented holistic and unbiased manner with hypothesis-free strategies.

Integrative Metabolomics Reveals Deep Tissue and Systemic Metabolic Remodeling in Glioblastoma.

(1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension. The mean survival is between 15 to 17 months. Given this aggressive prognosis, there is an urgent need for a better understanding of the underlying mechanisms of glioblastoma to unveil new diagnostic strategies and therapeutic targets through a deeper understanding of its biology. (2) Methods: To systematically address this issue, we performed targeted and untargeted metabolomics-based investigations on both tissue and plasma samples from patients with glioblastoma. (3) Results: This study revealed 176 differentially expressed lipids and metabolites, 148 in plasma and 28 in tissue samples. Main biochemical classes include phospholipids, acylcarnitines, sphingomyelins, and triacylglycerols. Functional analyses revealed deep metabolic remodeling in glioblastoma lipids and energy substrates, which unveils the major role of lipids in tumor progression by modulating its own environment. (4) Conclusions: Overall, our study demonstrates in situ and systemic metabolic rewiring in glioblastoma that could shed light on its underlying biological plasticity and progression to inform diagnosis and/or therapeutic strategies.

Intraventricular Hemorrhage in Very Preterm Infants: A Comprehensive Review.

Germinal matrix-intraventricular-intraparenchymal hemorrhage (GMH-IVH-IPH) is a major complication of very preterm births before 32 weeks of gestation (WG). Despite progress in clinical management, its incidence remains high before 27 WG. In addition, severe complications may occur such as post-hemorrhagic hydrocephalus and/or periventricular intraparenchymal hemorrhage. IVH is strongly associated with subsequent neurodevelopmental disabilities. For this review, an automated literature search and a clustering approach were applied to allow efficient filtering as well as topic clusters identification. We used a programmatic literature search for research articles related to intraventricular hemorrhage in preterms that were published between January 1990 and February 2020. Two queries ((Intraventricular hemorrhage) AND (preterm)) were used in PubMed. This search resulted in 1093 articles. The data manual curation left 368 documents that formed 12 clusters. The presentation and discussion of the clusters provide a comprehensive overview of existing data on the pathogenesis, complications, neuroprotection and biomarkers of GMH-IVH-IPH in very preterm infants. Clinicians should consider that the GMH-IVH-IPH pathogenesis is mainly due to developmental immaturity of the germinal matrix and cerebral autoregulation impairment. New multiomics investigations of intraventricular hemorrhage could foster the development of predictive biomarkers for the benefit of very preterm newborns.

Ruptured Intracranial Aneurysm in a Neonate: Case Report and Review of the Literature.

BACKGROUND: Intracranial aneurysms (IAs) are exceptional in neonates accounting for less than 2% of all IAs occurring during the first decade of life. Little is known about this pathology in this specific population. Because of its scarcity and this specific age at onset, the treatment of IA in neonates is challenging. We describe a rare case of aneurysmal subarachnoid hemorrhage in a neonate and review the current literature. CASE DESCRIPTION: A 21-day-old boy was admitted for hypotonia, vomiting, and seizures. Computed tomography scan revealed a subarachnoid hemorrhage in the sylvian fissure, a frontoparietal subdural hematoma, a left middle cerebral artery (MCA) aneurysm with a diameter of 11 mm, and an infarct of the MCA frontal region. He was successfully treated with endovascular coiling, neuroprotection, and antiepileptic drugs. Immediate postoperative magnetic resonance imaging showed a good aneurysm occlusion without any further ischemia. The outcome was favorable with extubation at day 10. At follow-up, the child experienced normal psychomotor development with no motor deficit. CONCLUSIONS: Ruptured IAs in neonates are rare. Subarachnoid hemorrhage is the most common presentation. Intracranial aneurysms are frequently larger than 10 mm and located on the MCA. The treatment could be surgical or endovascular depending on the characteristics of the aneurysm. There is no recommendation concerning the prevention or treatment of vasospasm in neonates.

Brain abscess in children, a two-centre audit: outcomes and controversies.

OBJECTIVE: The aim of this study was to better characterise clinical presentation, management and outcome in infants and children with brain abscess. METHODS: The authors conducted a retrospective, multicentre study in two national reference centres over a 25-year period (1992-2017). During this period, 116 children and 28 infants (age <1 year) with brain abscess were treated. RESULTS: The median age at diagnosis was 101.5 (range: 13-213) months in children and 1 (0-11) month in infants. Significant differences were observed between children and infants. The most common predisposing factor was meningitis in infants (64% of cases vs 3% in children), while it was otolaryngology-related infection in children (31% of cases vs 3.6% in infants). Infants presented more frequently with fever and meningism compared with children. 115 patients were treated with aspiration and 11 with excision. Reoperation was required in 29 children vs 1 infant. The overall mortality rate was 4% (3.4% for children, 7.1% for infants). At 3-month follow-up, the outcome was favourable in 86% of children vs in 68% of infants. CONCLUSION: There is a clear difference between children and infants with brain abscess in terms of predisposing factors, causative organisms and outcome. Despite surgical drainage and directed antibiotic therapy, 25% of patients with brain abscess require reoperation. Mortality is improved compared with historical series; however, long-term morbidity is significant particularly in the infant population.

Accuracy of the robot-assisted procedure in deep brain stimulation.

INTRODUCTION: The use of a robot-assisted technology becomes very competitive. The aim of this work was to define the accuracy of robotic assistance in deep brain stimulation surgery and to compare results with that in the literature. METHODS: We retrospectively reviewed the accuracy of lead implantation in 24 consecutive patients who had robot-assisted (ROSA, Zimmer-Biomet) surgery for the treatment of movement disorders. Intended stereotactic coordinates (x, y, z) of contact 0 (the most distal contact at the tip of the electrode) of each definitive lead were compared with actual coordinates obtained by a postoperative CT scan. For each lead, the euclidian 3D distance between the actual and intended location of contact 0 was calculated. RESULTS: The euclidian 3D distances between the intended and actual location of the contact 0 were 0.81 mm on the right side and 1.12 mm on the left side. DISCUSSION: Robot-assisted technology for stereotactic surgery is safe and accurate. The association with a 3D flat-panel CT scan is an optimized procedure for deep intracranial electrode implantation.

Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas.

The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. We report here the case of a young patient without any remarkable familial medical history who was first referred at 7 years of age, for an autism spectrum disorder (ASD) of Asperger type, not associated with macrocephaly. The patient subsequently presented at 10 years of age with multiple nodular lesions located within the trigeminal, facial and acoustic nerve ganglia and at the L3 level. Histological examination of this latter lesion revealed a glioneuronal hamartoma, exhibiting heterogeneous PTEN immunoreactivity, astrocyte and endothelial cell nuclei expressing PTEN, but not ganglion cells. NGS performed on the hamartoma allowed the detection of a PTEN pathogenic variant in 30% of the reads. The presence of this variant in the DNA extracted from blood and buccal swabs in 3.5 and 11% of the NGS reads, respectively, confirmed the mosaic state of the PTEN variant. The anatomical distribution of the lesions suggests that the mutational event affecting PTEN occurred in neural crest progenitors, thus explaining the absence of macrocephaly. This report shows that mosaic alteration of PTEN may result in multiple central and peripheral nervous system hamartomas and that the presence of such alteration should be considered in patients with multiple nervous system masses, even in the absence of cardinal features of PTEN hamartoma tumor syndrome, especially macrocephaly.

Intraventricular hemorrhage related to AVM rupture: Description, outcomes and impact of intraventricular fibrinolysis.

OBJECTIVES: Arteriovenous malformation (AVM) rupture could lead to intraventricular hemorrhage (IVH), a particularly severe form of intracranial bleeding. The epidemiology, presentation, management and outcomes of IVH related to AVM rupture have not been clearly addressed yet. The aim of the present study was to investigate the characteristics of IVH related to AVM rupture, with particular attention paid to functional outcomes and to the impact of intraventricular fibrinolysis (IVF). PATIENTS AND METHODS: Between 2011 and 2015, all patients suffering from IVH admitted in two tertiary neurosurgical centers were included in a prospective register. Patient with IVH related to AVM rupture were identified (n=29) and their data retrospectively collected. Particular attention was paid on patients who received IVF. We also compared them to 29 apparied aneurysmal IVH. RESULTS: IVH related to AVM rupture often occurred in young patients. In most cases, intracerebral hemorrhage was associated to IVH. 17% of the patients died, and functional outcome at 6 months was similar to those with aneurysmal IVH. Interestingly, 5 patients received IVF and none experienced any rebleeding. CONCLUSION: IVH related to AVM rupture is a severe form of hemorrhagic stroke, with a poor neurologic prognosis. IVF seems to be safe and may be considered in this particular form of IVH.