The Largest Germline Heterozygous Deletion Encompassing Potocki-Shaffer and WAGR Syndromes Loci to Date: A Case Report.

Potocki-Schaffer syndrome includes multiple exostoses, parietal foramina, and variable developmental delay/intellectual disability. It is associated with a heterozygous deletion of the 11p12p11.2 region. In some cases, the deletion extends to the WAGR locus (11p13p12). We describe here a 9-month-old girl harboring the largest germline heterozygous deletion characterized so far. Oligohydramnios and parietal foramina were noticed during pregnancy. No patient has been diagnosed before with concomitance of these two syndromes during the prenatal period. Cytogenetic diagnosis was anticipated on basis of clinical and radiological signs. Postnatal conventional karyotype confirmed an interstitial 11p deletion: 46,XX,del(11)(p11.2p15.1). Array-comparative genomic hybridization characterized a 29.6 Mb deletion. Our case illustrates the interest of high-resolution genomic approaches to correlate adequately clinical phenotypes with specific genes in suspected contiguous gene deletion syndromes.

Prone Positioning for Severe Acute Respiratory Distress Syndrome in COVID-19 Patients by a Dedicated Team: A Safe and Pragmatic Reallocation of Medical and Surgical Work Force in Response to the Outbreak.

OBJECTIVE: The aim of this study was to define whether rapidly reallocating health care workers not experienced with PP for performing PP in ICU is feasible and safe. SUMMARY BACKGROUND DATA: In the setting of severe acute respiratory distress syndrome (ARDS), the use of prone and supine positioning procedures (PP) has been associated with improved oxygenation resulting in decreased mortality. Nevertheless, applying PP is time consuming for ICU staffs that are at risk of mental of physical exhaustion, especially with the constant surge of admitted COVID-19 patients with severe ARDS. METHODS: This prospective cohort study conducted at a single regional university hospital between March 27 and April 15, 2020. Among 117 patients admitted to ICU, 67 patients (57.3%) presented with proven SARS-CoV-2 infection with severe ARDS requiring PP. After accelerated simulation training, 109 volunteers including surgeons, physicians, nurses and physiotherapists, multiple dedicated teams performed daily multiple PP following a systematic checklist. Patient demographics and PP data were collected. Patient safety and health care workers safety were assessed. RESULTS: Among 117 patients admitted to ICU, 67 patients (57.3%) required PP. Overall, 53 (79%) were male, with a median age of 68.5 years and median body mass index of 29.3 kg/m. A total of 384 PP were performed. Overall, complication occurred in 34 PP (8.8%) and led to PP cancelation in 4 patients (1%). Regarding health care workers safety, four health care workers presented with potential COVID-19 related symptoms and none was positive. CONCLUSIONS: To overcome the surge of critically ill COVID-19 patients, reallocating health care workers to targeted medical tasks beyond their respective expertise such as PP was safe.

A Giant Tumefactive Virchow-Robin Space: A Rare Cause of a Homonymous Quadrantanopia.

A 53-year-old woman was found to have a left inferior homonymous quadrantanopia. Brain MRI disclosed a giant Virchow-Robin space compressing the right optic tract. After fenestration of this cystic lesion, most of the visual field loss resolved. Giant Virchow-Robin spaces may cause homonymous field defects which, with appropriate management, may improve.

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease.

BACKGROUND: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. SUMMARY: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. KEY MESSAGE: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.

Indications for surgical evacuation of cerebellar intracerebral hemorrhage: consensus guidelines from the French Society of Neurosurgery (SFNC) and the French Society of Vascular Neurology (SFNV).

BACKGROUND: Cerebellar intracerebral hemorrhage (ICH) is associated with poor functional prognosis and high mortality. Surgical evacuation has been proposed to improve outcome. The purpose of this review was to determine the benefit of surgical evacuation of cerebellar ICH and to establish guidelines for when it should be performed. METHOD: The writing committee comprised 9 members of the SFNV and the SFNC. Recommendations were established based on a literature review using the PICO questions. The American Heart Association (AHA) classification was used to define recommendation level. In case of insufficient evidence, expert opinions were provided. RESULTS: Levels of evidence were low to moderate, precluding definitive recommendations. Based on available data, surgical hematoma evacuation is not recommended to improve functional outcome (Class III; Level B NR). However, based on subgroup analysis, surgical evacuation may be considered in strictly selected patients (Class IIb; Level C-EO): hematoma volume 15-25 cm3, GCS 6-10, and no oral anticoagulation or antiplatelet therapy. Moreover, surgical evacuation is recommended to decrease risk of death (Class IIa; Level B NR) in patients with a hematoma volume >15 cm3 and GCS score <10. CONCLUSION: These guidelines were based on observational studies, limiting the level of evidence. However, except for strictly selected patients, surgical evacuation of cerebellar ICH was not associated with improved functional outcome, limiting indications. Data from RCTs are needed in this field.

Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

BACKGROUND: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients. METHODS: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients. RESULTS: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%). CONCLUSIONS: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs.

Surgery for unruptured intracranial aneurysms in the ISAT and ISUIA era.

BACKGROUND: The ISAT and ISUIA studies, along with the improvement of endovascular treatment (EVT) have strongly influenced the management of intracranial aneurysms (IAs). We present our experience in the microsurgical treatment of unruptured IAs (UIAs) in this context. METHODS: We retrospectively reviewed a consecutive series of non-giant UIAs selected for surgery during a five-year period. Patients and aneurysms characteristics, surgical results and outcome assessed by the Glascow Outcome Scale (GOS) at three month follow-up were studied. RESULTS: Eighty-five patients underwent 93 surgical procedures to obliterate 113 UIAs. Those were incidental in 89% of the cases and mainly located on the middle cerebral artery (65%). Patients were assigned to surgery according to their medical history (young, previous subarachnoid haemorrhage), aneurysm characteristics (wide neck, branch at the neck, "small" size, associated "surgical" aneurysm) or failure of EVT (5%). Operatively, 48% of UIAs had thin wall or blebs and 71% were occluded with one titanium clip. Thrombectomy or temporary clipping were necessary in 4% and 11% of the cases, three aneurysms peroperatively ruptured, four were deemed unclippable, three paraclinoid UIAs had an intracavernous residue and 16% were wrapped because of a small neck remnant (class 2). The mortality rate was 0% and 4% of the patients experienced a definitive major neurological deterioration. Final GOS was unchanged in 96% of the patients. CONCLUSIONS: Despite reduction in operative cases and in appropriately selected patients ineligible to EVT, microsurgical clipping of non-giant anterior circulation UIAs can still achieve good outcome with very low mortality and neurological morbidity.

Decompressive surgery for malignant middle cerebral artery infarcts: the results of randomized trials can be reproduced in daily practice.

BACKGROUND: In clinical randomized controlled trials (RCTs), decompressive surgery (DS) for malignant middle cerebral artery (MMCA) infarcts leads to a 50% absolute risk reduction in mortality, and improves the 1-year functional outcome. The reproducibility of these results in routine practice has never been evaluated. The purpose of this study was to test the hypothesis that the results of DS for MMCA in practice are similar to those observed in the surgical group of RCTs. METHODS: We prospectively included the first 31 patients who underwent DS for MMCA. They were screened based on similar criteria as in the meta-analysis. The primary outcome was a modified Rankin Scale (mRS) score of ≤4, and secondary outcomes were mRS of ≤3 and death at 1 year. RESULTS: Thirty-one patients underwent DS for MMCA. The 1-year mRS was ≤4 in 22 patients (71.0%) and ≤3 in 16 (51.6%). Seven patients died (22.6%). CONCLUSION: This observational study showed that DS for MMCA in a center without previous experience provides similar results as those obtained in the surgical arm of RCTs.

Relevance of expandable titanium cage for the treatment of cervical spondylotic myelopathy.

BACKGROUND: In patients with cervical spondylotic myelopathy, ventral disease and loss of physiological cervical lordosis are indications for anterior approach. As bone graft and titanium cage present many drawbacks, expandable titanium cage has been recently introduced for this indication. The authors present the clinical and radiological outcomes in patients undergoing the placement of an expandable cage in the treatment of spondylotic myelopathy with straight or kyphotic cervical spine alignment. METHODS: This was a retrospective review of prospectively collected data. A total of 26 patients underwent cervical corpectomy and reconstruction using an expandable titanium cage and anterior plate between 2005 and 2008. Pain and functional disability were measured using VAS and mJOA preoperatively and at 3 months, 6 months, 1 year and 2 years. Kyphosis was measured using lateral radiographs at the same points of follow-up. Fusion was evaluated on flexion-extension radiographs at 2 years. RESULTS: The mean VAS improved from 4.2 to 1.7 and the mean mJOA increased from 12.85 to 16.04 at 2 years postoperatively (p < 0.05). The mean kyphosis angle decreased from 17° to 2° at the last follow-up (p < 0.05). The fusion rate was 100% at 2 years. Three complications were reported including a transient dysphagia, an epidural hematoma and an early hardware migration. CONCLUSION: Expandable titanium cage is an effective device, which achieves good clinical and radiological outcomes at a minimum 2-year follow-up.

Management of delayed oesophagus perforation and osteomyelitis after cervical spine surgery: review of the literature.

Oesophagus perforation is a possible complication of anterior cervical spine surgery, which generally occurs during the first postoperative days. Delayed perforation is very rare and its management remains controversial. We report the successful management of a delayed oesophagus perforation associated with an osteomyelitis.

Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.

INTRODUCTION: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. METHODS AND ANALYSIS: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

Retrosigmoid approach for meningiomas of the cerebellopontine angle: results of surgery and place of additional treatments.

BACKGROUND: Meningiomas of the cerebellopontine angle (CPA), although homogenous in terms of location, present different surgical challenges depending on their site of dural origin and extension. Complete tumor resection sometimes leads to high morbidity. The objective of this work is to evaluate the results of surgery and the place of additional treatments. METHODS: In a series of 115 patients with CPA meningiomas, we retrospectively studied 69 patients operated on between 1994 and 2007 using a retrosigmoid approach. Clinical presentation, operative findings and functional outcome were reviewed for a mean follow-up time of 36 months. RESULTS: Usual presentation was hearing loss associated with gait disturbance (50%) and vertigo (35%). Preoperative cochlear evaluation was abnormal in 40% of the cases. Most tumors (90%) originated on the posterior face of the petrous part of the temporal bone. In one-third of the cases, the meningioma had invaded the internal acoustic meatus. Total or subtotal tumor removal was achieved in 91% of patients without perioperative mortality. Fourteen patients received additional treatment with radiotherapy or radiosurgery for a small residual tumor, often deliberately left in place to reduce operative morbidity. At long-term follow-up, facial nerve function was preserved in 91% of the cases. Hearing worsened in 17% of patients. The tumor recurred in only one case. CONCLUSION: The retrosigmoid approach is a safe surgical procedure. The modern management of CPA meningiomas should achieve as complete a resection as possible within reasonable limits, considering that a small residual tumor can be controlled fairly easily with radiosurgery for a relatively long time.

Ruptured cerebral oncotic aneurysm from choriocarcinoma: report of two cases and review of the literature.

The study design involved case reports and review of the literature. Oncotic aneurysm from choriocarcinoma is an extremely rare event that should be known by all neurosurgeons and suspected in women of childbearing age. The purpose of this article is to report the authors' experience and to provide insight on clinical presentation and radiological signs to aware the reader to this entity and then to prevent misdiagnosis. The authors report two cases of ruptured oncotic aneurysm treated at their institution in 2010. A review of the literature was performed to discuss the pathogenesis and the role of the neurosurgeon. Chemotherapy is the treatment of choice making surgery necessary only for patients with large intracerebral haematoma that represents an immediate threat.

Subacute involvement of the medulla oblongata and occipital neuralgia revealing an intracranial dural arteriovenous fistula of the craniocervical junction.

A 58-year-old woman with cervicomedullary dural arteriovenous fistula (AVF) presenting with myelopathy, ipsilateral occipital neuralgia, and signs of involvement of the brainstem is reported and the previously published cases have been reviewed. The dural AVF was successfully treated surgically after an attempt of embolization.

Spinal cord herniation: a misdiagnosed and treatable cause of thoracic myelopathy.

This study is a case report and review of the literature. Spinal cord herniation is a rare, although increasingly recognized, cause of spinal cord dysfunction. It is due to an anterior dural defect, through which the spinal cord herniates. The purpose of this article is to report the authors' experience and to provide insight on clinical presentation and radiological signs to make the reader aware of this entity and then to prevent misdiagnosis. The authors conducted a retrospective review of patients who underwent surgery for spinal cord herniation at their institution between 2000 and 2008. Three patients were treated (all women) and the interval between the onset of symptoms and surgery ranged from 24 to 48 months. All patients had progressive signs of thoracic myelopathy, and two of them were initially misdiagnosed. In all cases, the herniation was reduced and the defect repaired using different methods. The results and complications of our cases were compared with that of the reported literature. According to the results in these cases and the review of the literature, the authors believe that spinal cord herniation should be treated by using a dural patch to close the dural defect and to prevent retethering of the spinal cord.

Ultra-early rebleeding of an anterior spinal artery aneurysm.

The authors report the case of a 38-year-old patient who presented with a ruptured anterior spinal artery aneurysm confirmed by MRI. This patient harbored neurological deterioration related to a rebleeding at Day 1. Control angiography showed spontaneous occlusion of both aneurysm and distal anterior spinal axis. Expectative strategy was finally chosen because of the rebleeding. However, these spinal aneurysms must be treated urgently because of the risk of ultra-early rebleeding.

A Survey of Microsurgical Technique for Extracranial-to-Intracranial Bypass.

BACKGROUND: Extracranial-to-intracranial bypass surgery is a well-established technique that has been practiced for over 50 years. Since then, numerous technical variants have developed nationally and internationally. OBJECTIVE: Based on a survey, to collect information on cerebrovascular bypass surgeons and their background, surgical volume, and technical steps of extracranial-to-intracranial bypasses with focus on superficial temporal artery to middle cerebral artery (STA-MCA) bypass. METHODS: An electronic survey was distributed among bypass neurosurgeons. Responses were analyzed for national-international variations of STA-MCA bypass surgery techniques. The survey focused on the technical aspects of the surgery itself rather than patient selection or perioperative management. RESULTS: Survey responses were collected from 51 neurosurgeons performing cerebrovascular bypass, from 11 different countries across North America, Europe, and Asia. The largest age block was early-to mid-career (66.7% aged 36-50 years). Most participating surgeons (80.40%) performed less than 20 bypasses annually, whereas a select few surgeons (3) performed more than 50 annually. The most common bypass was STA-M4 MCA bypass with a linear incision (34%) over the parietal branch (44%) and choosing an MCA recipient based on diameter (61.2%). The interrupted anastomosis technique was most common (74%). CONCLUSIONS: The results of this electronic survey will help to identify common patterns in STA-MCA bypass surgery and will serve as a guide to other neurosurgeons to modify and improve their technique. Cerebrovascular bypass is still widely practiced, including by young neurosurgeons, who are actively learning from established masters who share their experience.

Intraoperative biplanar rotational angiography during neurovascular surgery. Technical note.

OBJECT: The purpose of this study was to evaluate the authors' initial experience with the integration of high-resolution rotational and biplanar angiography during neurovascular operative procedures. METHODS: Eight patients with intracerebral arteriovenous malformations (AVMs) and aneurysms underwent surgical treatment of their lesions in a combined endovascular surgical suite. After initial head positioning, preoperative biplane and rotational angiography was performed. Resection of the AVM or clipping of the aneurysm was then performed. Further biplane and rotational 3D angiograms were obtained intraoperatively to confirm satisfactory treatment. RESULTS: One small residual AVM identified intraoperatively necessitated further resection. One aneurysm was clipped during endovascular inflation of an intracarotid balloon for temporary proximal control. The completeness of treatment was confirmed on intraoperative 3D rotational angiography in all cases, and there were no procedure-related complications. CONCLUSIONS: Intraoperative rotational angiography performed in an integrated biplane angiography/surgery suite is a safe and useful adjunct to surgery and may enable combining endovascular and surgical procedures for the treatment of complex vascular lesions.

Assessment of extracranial-intracranial bypass patency with 64-slice multidetector computerized tomography angiography.

INTRODUCTION: Extracranial-intracranial (EC/IC) bypass is a useful procedure for the treatment of cerebral vascular insufficiency or complex aneurysms. We explored the role of multidetector computed tomography angiography (MDCTA), instead of digital subtraction angiography (DSA), for the postoperative assessment of EC/IC bypass patency. METHODS: We retrospectively analyzed a consecutive series of 21 MDCTAs from 17 patients that underwent 25 direct or indirect EC/IC bypass procedures between April 2003 and November 2007. Conventional DSA was available for comparison in 13 cases. MDCTA used a 64-slice MDCT scanner (Aquilion 64, Toshiba). The proximal and distal patencies were analyzed independently on MDCTA and DSA by a neuroradiologist and a neurosurgeon. The bypass was considered patent when the entire donor vessel was opacified without discontinuity from proximal to distal ends and was visibly in contact with the recipient vessel. RESULTS: MDCTA depicted the patency status in every patient. Bypasses were patent in 22 cases, stenosed in one, and occluded in two. DSA always confirmed the results of the MDCTA (sensitivity = 100%, 95% CI = 0.655-1.0; specificity 100%, 95% CI = 0.05-1.0). CONCLUSIONS: MDCTA is a non-invasive and accurate exam to assess the postoperative EC/IC bypass patency and is a promising technique in routine follow-up.

GDC 360 degrees for the endovascular treatment of intracranial aneurysms: a matched-pair study analysing angiographic outcomes with GDC 3D Coils in 38 patients.

INTRODUCTION: The purpose of this study was to determine whether coil embolisation with a new complex-shaped Guglielmi Detachable Coil (GDC 360 degrees; Boston Scientific Neurovascular, Fremont, CA, USA) has any effect on the stability of aneurysm occlusion. MATERIALS AND METHODS: Fifty-one consecutive patients with intracranial aneurysms treated with GDC 360 degrees were included. Angiographic results and adverse neurological events during the follow-up period were recorded. For 38 patients treated with GDC 360 degrees with available follow-up data, a corresponding patient treated with GDC 3D was identified from our database. Matches were sought for rupture status, location, aneurysmal size, and neck size. The angiographic outcome of these matched controls at 6 months was compared to aneurysms treated with GDC 360 degrees. RESULTS: Initial angiographic controls for 38 patients treated with GDC 360 degrees showed complete occlusion in 32 aneurysms, and a neck remnant in six. At 6-month follow-up, complete occlusion was found in 29, a neck remnant in eight, and a residual aneurysm in one. One patient treated with GDC 360 degrees needed retreatment for a major recanalisation. In 38 matched patients treated with GDC 3D, initial angiographic controls found complete aneurysmal occlusion in 30 aneurysms and a residual neck in 8. At 6-month follow-up, 24 aneurysms were completely occluded, ten showed a neck remnant, and residual aneurysms were seen in four. Four patients, treated with GDC 3D, were retreated for major aneurysm recanalisations. CONCLUSION: Our data suggests that endovascular coil embolisation with GDC 360 degrees might improve long-term stability of coiled aneurysms when compared to GDC 3D.