A Bispecific, Tetravalent Antibody Targeting Inflammatory and Pruritogenic Pathways in Atopic Dermatitis.

Inhibition of IL-4/IL-13 signaling has dramatically improved the treatment of atopic dermatitis (AD). However, in many patients, clinical responses are slow to develop and remain modest. Indeed, some symptoms of AD are dependent on IL-31, which is only partially reduced by IL-4/IL-13 inhibition. Thus, there is an unmet need for AD treatments that concomitantly block IL-4/IL-13 and IL-31 pathways. We engineered NM26-2198, a bispecific tetravalent antibody designed to accomplish this task. In reporter cell lines, NM26-2198 concomitantly inhibited IL-4/IL-13 and IL-31 signaling with a potency comparable with that of the combination of an anti-IL-4Rα antibody (dupilumab) and an anti-IL-31 antibody (BMS-981164). In human PBMCs, NM26-2198 inhibited IL-4-induced upregulation of CD23, demonstrating functional binding to FcγRII (CD32). NM26-2198 also inhibited the secretion of the AD biomarker thymus and activation-regulated chemokine (TARC) in blood samples from healthy human donors. In male cynomolgus monkeys, NM26-2198 exhibited favorable pharmacokinetics and significantly inhibited IL-31-induced scratching at a dose of 30 mg/kg. In a repeat-dose, good laboratory practice toxicology study in cynomolgus monkeys, no adverse effects of NM26-2198 were observed at a weekly dose of 125 mg/kg. Together, these results justify the clinical investigation of NM26-2198 as a treatment for moderate-to-severe AD.

[Spinal injury related to alpine winter sports]. / Fractures de la colonne vertébrale lors d'accidents de ski ou autres sports de neige.

Winter sports are the cause of a significant number of spinal injuries in Switzerland. However, the number of patients, the mechanism, the presentation, the diagnosis and the treatment of vertebral fractures have considerably evolved over the last decades. As the hospital of Sion, in Valais, is particularly exposed to these diagnoses, we analyzed two series of prospective cases 30 years apart (1989-1990 and 2019-2020) and propose a review of the main types and mechanisms of fractures, diagnosis, and management for the primary care physician.

Les sports d'hiver sont à l'origine d'un nombre important de lésions de la colonne vertébrale en Suisse. Cependant, le nombre de patients, le mécanisme, la présentation, le diagnostic et le traitement des fractures vertébrales ont considérablement évolué au cours des dernières décennies. L'hôpital de Sion, en Valais, étant particulièrement exposé à ces diagnostics, nous avons analysé deux séries de cas prospectives à 30 ans d'intervalle (1989-1990 et 2019-2020) et proposons une revue des principaux types et mécanismes de fractures, diagnostics, et prises en charge pour le médecin de premier recours.

An engineered T-cell engager with selectivity for high mesothelin-expressing cells and activity in the presence of soluble mesothelin.

Mesothelin (MSLN) is an attractive immuno-oncology target, but the development of MSLN-targeting therapies has been impeded by tumor shedding of soluble MSLN (sMSLN), on-target off-tumor activity, and an immunosuppressive tumor microenvironment. We sought to engineer an antibody-based, MSLN-targeted T-cell engager (αMSLN/αCD3) with enhanced ability to discriminate high MSLN-expressing tumors from normal tissue, and activity in the presence of sMSLN. We also studied the in vivo antitumor efficacy of this molecule (NM28-2746) alone and in combination with the multifunctional checkpoint inhibitor/T-cell co-activator NM21-1480 (αPD-L1/α4-1BB). Cytotoxicity and T-cell activation induced by NM28-2746 were studied in co-cultures of peripheral blood mononuclear cells and cell lines exhibiting different levels of MSLN expression, including in the presence of soluble MSLN. Xenotransplant models of human pancreatic cancer were used to study the inhibition of tumor growth and stimulation of T-cell infiltration into tumors induced by NM28-2746 alone and in combination with NM21-1480. The bivalent αMSLN T-cell engager NM28-2746 potently induced T-cell activation and T-cell mediated cytotoxicity of high MSLN-expressing cells but had much lower potency against low MSLN-expressing cells. A monovalent counterpart of NM28-2746 had much lower ability to discriminate high MSLN-expressing from low MSLN-expressing cells. The bivalent molecule retained this discriminant ability in the presence of high concentrations of sMSLN. In xenograft models, NM28-2746 exhibited significant tumor suppressing activity, which was significantly enhanced by combination therapy with NM21-1480. NM28-2746, alone or in combination with NM21-1480, may overcome shortcomings of previous MSLN-targeted immuno-oncology drugs, exhibiting enhanced discrimination of high MSLN-expressing cell activity in the presence of sMSLN.

Traumatic Brain Injury in Alpine Winter Sports: Comparison of Two Case Series from a Swiss Trauma Center 30 Years Apart.

BACKGROUND: Between 3 and 15% of winter sports-related injuries are related to head injuries, which are the primary cause of mortality and disability among skiers. Despite the widespread adoption of helmets in winter sports, which has reduced the incidence of direct head injury, there is a paradoxical trend of an increasing number of individuals wearing helmets sustaining diffuse axonal injuries (DAI), which can result in severe neurologic sequelae. METHODS: We retrospectively reviewed 100 cases collected by the senior author of this work from 13 full winter seasons during the period from 1981 to 1993 and compared them with 17 patients admitted during the more shortened 2019 to 2020 ski season due to COVID-19. All data analyzed come from a single institution. Population characteristics, mechanism of injury, helmet use, need for surgical treatment, diagnosis, and outcome were collected. Descriptive statistics were used to compare the two databases. RESULTS: From February 1981 to January 2020, most skiers with head injuries were men (76% for the 1981-1993 and 85% for 2020). The proportion of patients aged over 50 increased from <20% in 1981 to 65% in 2020 (p < 0.01), with a median age of 60 years (range: 22-83 years). Low- to medium-velocity injuries were identified in 76% (13) of cases during the 2019 to 2020 season against 38% (28/74) during the 1981 to 1993 seasons (p < 0.01). All injured patients during the 2020 season wore a helmet, whereas none of the patients between 1981 and 1993 wore one (p < 0.01). DAI was observed in six cases (35%) for the 2019 to 2020 season against nine cases (9%) for the 1981 to 1993 season (p < 0.01). Thirty-four percent (34) of patients during the 1981 to 1993 seasons and 18% (3) of patients during the 2019 to 2020 season suffered skeletal fractures (p = 0.02). Among the 100 patients of the 1981 to 1993 seasons, 13 (13%) died against 1 (6%) from the recent season during care at the hospital (p = 0.15). Neurosurgical intervention was performed in 30 (30%) and 2 (12%) patients for the 1981 to 1993 and 2019 to 2020 seasons, respectively (p = 0.003). Neuropsychological sequelae were reported in 17% (7/42) of patients from the 1981 to 1993 seasons and cognitive evaluation before discharge detected significant impairments in 24% (4/17) of the patients from the 2019 to 2020 season (p = 0.29). CONCLUSION: Helmet use among skiers sustaining head trauma has increased from none in the period from 1981 to 1993 to 100% during the 2019 to 2020 season, resulting in a reduction in the number of skull fractures and deaths. However, our observations suggest a marked shift in the type of intracranial injuries sustained, including a rise in the number of skiers experiencing DAI, sometimes with severe neurologic outcomes. The reasons for this paradoxical trend can only be speculated upon, leading to the question of whether the perceived benefits of helmet use in winter sports are actually misinterpreted.

Reducing the learning curve of interlaminar full-endoscopic discectomy: mushroom model-simulation training.

PURPOSE: To describe a cheap simulation model used to reduce the learning curve of the interlaminar full-endoscopic discectomy in a pilot study. INTRODUCTION: The steep and difficult learning curve remain one of the main obstacles against the widespread diffusion of interlaminar full endoscopic lumbar discectomy (ILFED). One solution to overcome this learning curve is training with deliberate practice. As realistic models are relatively expensive and cadaver workshops not readily available, we developed a simple and cheap model to train the key steps of the procedure. METHODS: A simple and cheap model were designed. It consists of a king oyster mushroom stalk, a glove finger, a sponge and cotton wool. In order to fix the model to the table and to simulate the level of the patient's skin whereupon the hand of the surgeon relies, a wooden holding device was also used. As the purpose of this pilot study was to evaluate the model as a stimulator, it was tested during an advanced endoscopic training course. RESULTS: A step-by-step learning method with key steps was used by participants attending an advanced ILFED training on expensive realistic models. The model was considered as comparable and enough realistic to train key steps in order to reduce the learning curve and training costs. CONCLUSION: We present an affordable, simple and reproducible training model, which allows for deliberate practice of the key steps of the ILFED procedure. The model may be used by surgeons starting with spinal endoscopy.

Late metachronous cerebral metastasis of pancreatic adenocarcinoma of the tail of the pancreas: a case report.

BACKGROUND: Pancreatic cancer is one of the leading causes of cancer mortality and one of the most lethal malignant neoplasms worldwide. It is known for its local tumor extension to the liver; other common sites include the lung, distant lymph nodes, and bone. Brain metastases are extremely rare and represent less than 0.6% of all brain metastases. CASE REPORT: We report the case of a 66-year-old Caucasian female known to have adenocarcinoma of the tail of the pancreas treated with chemotherapy. During follow-up, thoracoabdominal computed tomography scans did not reveal any residual tumor or any metastasis. Moreover, tumor markers were within normal limits. She presented to the emergency department of our institution following an episode of a generalized tonic-clonic seizure 5 years following the initial diagnosis. Brain magnetic resonance imaging revealed an expansive left frontal intraaxial lesion compatible with high-grade glioma. The patient underwent surgical treatment. Histological examination revealed pancreatic metastasis. CONCLUSIONS: Thought to be rare, metachronous cerebral pancreatic metastasis should be kept in mind in patients with pancreatic cancer. Early diagnosis and complete surgical resection play a key role in the survival of these patients.

Delayed oculomotor nerve palsy associated with a ruptured anterior communicating aneurysm: Case report.

BACKGROUND AND IMPORTANCE: Oculomotor nerve palsy (ONP) is usually associated with posterior communicating (PCOM) aneurysms. ONP in patients with anterior circulation aneurysms are extremely rare, with only a handful of such published cases to date. There is currently no accepted mechanism to explain this clinical finding. CLINICAL PRESENTATION: We describe a case of a 60-year-old female that benefitted from endovascular coiling of a ruptured anterior communicating (ACOM) aneurysm. In the following days, she clinically deteriorated and benefitted from another digital subtraction angiography (DSA) with intravascular verapamil for suspected vasospasm, and subsequently developed a right ONP. CONCLUSION: Although classically related to PCOM aneurysm, ONP may be associated with ACOM aneurysms. The causative mechanism is unclear, but vasospasm may alter the microvascularisation of the oculomotor nerve, leading to ischemia.

Full-Endoscopic Resection of a Recurrent Posterior Longitudinal Ligament Cyst: Technical Note.

BACKGROUND: Posterior longitudinal ligament cysts are very rare lesions and do not usually recur. Microscopic resection is commonly performed. The aim of this article was to report a case of recurrent posterior longitudinal ligament cyst that benefited from full-endoscopic resection. METHODS: We used the 25° endoscope of the RIWOspine set for interlaminar approach. A step-by-step description of the surgical technique was presented. RESULTS: Clinical evolution was favorable. The patient remained pain-free 1 month after surgery, and postoperative magnetic resonance imaging showed complete resection of the cyst. CONCLUSIONS: Endoscopy is a safe and feasible approach for posterior longitudinal ligament cysts, including unusual recurrent cases.

Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade.

Co-stimulatory 4-1BB receptors on tumor-infiltrating T cells are a compelling target for overcoming resistance to immune checkpoint inhibitors, but initial clinical studies of 4-1BB agonist mAbs were accompanied by liver toxicity. We sought to engineer a tri-specific antibody-based molecule that stimulates intratumoral 4-1BB and blocks PD-L1/PD-1 signaling without systemic toxicity and with clinically favorable pharmacokinetics. Recombinant fusion proteins were constructed using scMATCH3 technology and humanized antibody single-chain variable fragments against PD-L1, 4-1BB, and human serum albumin. Paratope affinities were optimized using single amino acid substitutions, leading to design of the drug candidate NM21-1480. Multiple in vitro experiments evaluated pharmacodynamic properties of NM21-1480, and syngeneic mouse tumor models assessed antitumor efficacy and safety of murine analogues. A GLP multiple-dose toxicology study evaluated its safety in non-human primates. NM21-1480 inhibited PD-L1/PD-1 signaling with a potency similar to avelumab, and it potently stimulated 4-1BB signaling only in the presence of PD-L1, while exhibiting an EC50 that was largely independent of PD-L1 density. NM21-1480 exhibited high efficacy for co-activation of pre-stimulated T cells and dendritic cells. In xenograft models in syngeneic mice, NM21-1480 induced tumor regression and tumor infiltration of T cells without causing systemic T-cell activation. A GLP toxicology study revealed no evidence of liver toxicity at doses up to 140 mg/kg, and pharmacokinetic studies in non-human primates suggested a plasma half-life in humans of up to 2 weeks. NM21-1480 has the potential to overcome checkpoint resistance by co-activating tumor-infiltrating lymphocytes without liver toxicity.

A case of subependymal giant cell astrocytoma without tuberous sclerosis complex and review of the literature.

Subependymal giant cell astrocytoma (SEGA) is a World Health Organization (WHO) grade I tumor most commonly seen in the context of the underlying tuberous sclerosis complex (TSC). SEGA in the absence of TSC is exceedingly rare. We report the youngest known case of SEGA in the absence of genetic or phenotypic evidence of TSC with a 10-year follow-up. We discuss the literature surrounding isolated SEGA including an approach to diagnosis, management, and prognosis.

Surgical management of symptomatic cavum septum pellucidum cysts: systematic review of the literature.

Cavum septum pellucidum (CSP) and cavum vergae (CV) cysts are commonly found incidentally. They are usually asymptomatic but may present with symptoms related to obstructive hydrocephalus. There is no consensus about the management of symptomatic CSP and CV cysts. We present, to the best of our knowledge, the first systematic review of the different treatment options for symptomatic CSP and CV cysts. We conducted a literature review using PubMed database, searching for cases of symptomatic CSP and CV cysts managed surgically, and published until April 2019. Preoperative characteristics, surgical procedure, and postoperative outcome were analyzed using SPSS® software (Statistical Package for Social Sciences, IBM®). We found 54 cases of symptomatic CSP and CV cysts managed surgically (34 males, 20 females, 1.7/1 male to female ratio). Mean age was 24.3 ± 20.1 years. The most common presentation was headaches (34 patients, 62%), followed by psychiatric symptoms (27 patients, 49.1%). Preoperative radiological hydrocephalus was present in 30 patients (54.5%). The most common surgical procedure was endoscopic fenestration (39 patients, 70.9%), followed by shunting (10 patients, 18.2%), open surgery (3 patients, 5.5%), and stereotactic fenestration (1 patient, 1.8%). Complete resolution of symptoms was achieved in 36 patients (65.5%) and partial resolution in 7 patients (12.7%), and symptoms were unchanged in 2 patients. The present review suggests that surgical treatment could provide resolution of the symptoms in most of the cases, regardless of the procedure performed. Although mean follow-up was short among the studies, recurrence rate was low.

Endonasal endoscopic resection of suprasellar craniopharyngioma: A retrospective single-center case series.

INTRODUCTION: Endoscopic endonasal approach (EEA) has recently been proposed as an option for resection of primary and recurrent suprasellar craniopharyngioma. However, surgical outcome has not yet been fully evaluated, especially in regards to recurrent cases. METHODS: We analysed our institution (Sir Charles Gairdner University Hospital, Perth, Australia) case-series retrospectively. There were 16 patients operated through an endonasal endoscopic approach from February 2014 to February 2019 for suprasellar craniopharyngiomas. There were 14 primary, and two recurrent lesions. Extent of resection, complications, visual and endocrinological outcomes are presented. RESULTS: Mean age of the patients was 42.9 ± 19.3 years old, with 56% female. The most common clinical symptoms were headaches (9 patients, 56%) and bi-temporal hemianopsia (9 patients, 56%), followed by unilateral optic neuropathy (5 cases, 31%), memory loss (1 case, 6%), hydrocephalus (1 case, 6%), delayed growth and puberty (1 case, 6%), and secondary amenorrhoea (1 case, 6%). Only two cases (12%) initially presented with normal visual function. Gross total resection (GTR) was achieved in 10/16 patients (62.5%), with subtotal resection (STR) in the remainder. Visual symptoms improved in 13/16 patients (81%) and remained unchanged in 3/16 patients (19%). Most common complications included new endocrinological deficit in nine patients (56%), mostly diabetes insipidus, and cerebrospinal fluid leak requiring a new intervention in three patients (19%). There was one mortality case (complicated meningitis, stroke and vasospasm). Mean follow-up time was 22.05 ± 14 months and three patients (19%) had a recurrence of the disease during this period and were referred for radiation therapy. CONCLUSION: Endonasal endoscopic approach is a safe and effective surgical option for both primary and recurrent suprasellar craniopharyngiomas.

Prophylactic levetiracetam-induced pancytopenia with traumatic extra-dural hematoma: Case report.

BACKGROUND: Pancytopenia has only rarely been reported with Levetiracetam use. It is a potentially life threatening adverse effect that requires cessation of therapy. CASE DESCRIPTION: We describe a case of an otherwise well thirty-two-year-old man who underwent an emergent craniotomy for evacuation of a traumatic extra-dural haematoma. Post-operatively, he developed pancytopenia which corrected with cessation of levetiracetam. CONCLUSION: This report aims to increase awareness of this rare side effect and reiterates the judicious use of prophylactic levetiracetam in brain trauma.

Endoscopic Fenestration of Cavum Septum Pellucidum Cysts to the Third Ventricle: Technical Note.

BACKGROUND AND IMPORTANCE: Cavum septum pellucidum (CSP) and cavum vergae (CV) cysts are common incidental findings on imaging studies. However, they may rarely present with symptoms related to the obstruction of the foramen of Monro by the cyst leaflets. There is no consensus regarding the management of symptomatic CSP and CV cysts. We present an original transcavum interforniceal endoscopic fenestration technique. The step-by-step surgical procedure and two illustrative cases are presented. CLINICAL PRESENTATION: A 31-yr-old male and a 24-yr-old woman presented with symptomatic CSP and CV cysts. For both patients, neuronavigation was used to plan the procedure. An endoscope was introduced into the cyst through a right frontal burr-hole. After an examination of the endoscopic anatomy, a communication between the cyst and the third ventricle was performed using an endoscopic forceps. In both cases, directly after the fenestration, cerebrospinal fluid (CSF) passed through the communication, and the collapse of the cyst was appreciated. Symptoms were relieved in both patients, and neuropsychological assessment improved. Postoperative imaging showed a reduction in the cyst bulge, and patent foramen of Monro. CONCLUSION: Endoscopic fenestration of CSP and CV cysts to the third ventricle through an interforniceal navigated approach is a feasible and efficient surgical procedure. Theoretical advantages include a single tract through noneloquent brain, a perpendicular trajectory to the membrane for fenestration, and a large CSF space beyond the fenestration point.

Implementation of cisternostomy as adjuvant to decompressive craniectomy for the management of severe brain trauma.

OBJECTIVE: To evaluate the value of an adjuvant cisternostomy (AC) to decompressive craniectomy (DC) for the management of patients with severe traumatic brain injury (sTBI). METHODS: A single-center retrospective quality control analysis of a consecutive series of sTBI patients surgically treated with AC or DC alone between 2013 and 2018. A subgroup analysis, "primary procedure" and "secondary procedure", was also performed. We examined the impact of AC vs. DC on clinical outcome, including long-term (6 months) extended Glasgow outcome scale (GOS-E), the duration of postoperative ventilation, and intensive care unit (ICU) stay, mortality, Glasgow coma scale at discharge, and time to cranioplasty. We also evaluated and analyzed the impact of AC vs. DC on post-procedural intracranial pressure (ICP) and brain tissue oxygen (PbO2) values as well as the need for additional osmotherapy and CSF drainage. RESULTS: Forty patients were examined, 22 patients in the DC group, and 18 in the AC group. Compared with DC alone, AC was associated with significant shorter duration of mechanical ventilation and ICU stay, as well as better Glasgow coma scale at discharge. Mortality rate was similar. At 6-month, the proportion of patients with favorable outcome (GOS-E ≥ 5) was higher in patients with AC vs. DC [10/18 patients (61%) vs. 7/20 (35%)]. The outcome difference was particularly relevant when AC was performed as primary procedure (61.5% vs. 18.2%; p = 0.04). Patients in the AC group also had significant lower average post-surgical ICP values, higher PbO2 values and required less osmotic treatments as compared with those treated with DC alone. CONCLUSION: Our preliminary single-center retrospective data indicate that AC may be beneficial for the management of severe TBI and is associated with better clinical outcome. These promising results need further confirmation by larger multicenter clinical studies. The potential benefits of cisternostomy should not encourage its universal implementation across trauma care centers by surgeons that do not have the expertise and instrumentation necessary for cisternal microsurgery. Training in skull base and vascular surgery techniques for trauma care surgeons would avoid the potential complications associated with this delicate procedure.

Posterior wall acetabular fracture in a 13-year-old boy treated by open reduction and mini-plate internal fixation: long-term follow-up of 17 years.

BACKGROUND: Acetabular fractures are uncommon in children and adolescents, mainly because of predominant cartilaginous component and strong surrounding ligaments. Although acetabular fractures at this age can lead to significant disability, there is no consensus regarding management, which continues to be controversial. Particularly, long-term outcome after operative management has not been evaluated. CASE PRESENTATION: We report a case of a 13-year-old boy skeletally immature who presented with an isolated acetabular fracture involving the posterior wall secondary to a traumatic hip dislocation. A Kocher-Langenbeck approach with a surgical luxation of the hip was used for reduction and mini-plate internal fixation of the fracture. Long-term (17-year) follow-up showed a good clinical outcome and a good congruence of the. The patient has bilateral beginning osteoarthritis due to a cam configuration of both hips CONCLUSION: We describe a case of successful operative management of an acetabulum fracture in a skelettaly immature child with a long-term follow-up. Aggressive management of this rare type of fractures may lead to durable positive outcome.

Sudden Onset of Paraparesis Caused by a Hemorrhagic Thoracic Synovial Cyst.

BACKGROUND: Hemorrhage is a rare presentation of spinal synovial cysts, which are usually located in the lumbar spine. They may cause an epidural hematoma and compression of the cauda equina. Infrequently, they may be located in the thoracic spine. CASE DESCRIPTION: We present a case of sudden onset paraparesis caused by hemorrhage in a synovial cyst at a midthoracic level. Clinical, radiologic, and histologic findings are described. CONCLUSIONS: This report describes a unique case of hemorrhagic synovial cyst at the mid-thoracic spine. These lesions are rarely located in the cervico-thoracic spine but should be included in the differential diagnosis of myelopathy.

Correlation between Papilledema and Intracranial Hypertension in Crouzon Syndrome: A Case Report and Review of the Literature.

Crouzon syndrome represents the most common syndromic craniosynostosis. Ocular complications are frequent, including papilledema and optic atrophy, often related to increased intracranial pressure (ICP). However, there is a poor correlation between ICP normalization and resolution of papilledema. We describe the case of a 6-month-old infant who presented with typical phenotypic features of Crouzon syndrome. Pre- and postoperative ICP monitoring was used. Papilledema persisted despite ICP improvement after decompressive craniectomy. Possible causes of papilledema in this syndromic craniosynostosis are discussed in light of the existing literature.

Extra-Axial Cavernoma of the Cerebellopontine Angle: A Case Study and Review of Literature.

BACKGROUND: Extra-axial cavernoma (EAC) at the cerebellopontine angle (CPA) is a rare clinical entity that can mimic radiologically several lesions encountered at this location. We report a case of EAC-CPA and present a review of the literature. METHODS: A PubMed research was conducted looking for EAC-CPA lesions described in literature. After reviewing all the relevant articles, the following data were extracted and organized into a single table: patients' symptoms, radiological characteristics, surgical procedure, histopathology, and outcome. RESULTS: Eighteen cases (including ours) were identified from these reports. Mean age at diagnosis was 42 with a male:female ratio of 2.6:1. The most commonly involved cranial nerves were the vestibulocochlear complex followed by the trigeminal nerve. The lesions were iso-to hypodense on computed tomography. On magnetic resonance imaging, the EAC-CPA can be solid or cystic. All lesions were approached using retrosigmoid craniotomies. Histologically, both intra- and extra-axial cavernomas are identical, consisting of devoid vascular sinusoids with endothelial lining. The outcome was favorable in 16/18 of the described cases. One case presented a worsened facial paresis and 1 patient died from excessive intraoperative bleeding and subsequent complications. CONCLUSIONS: Despite the fact that EAC-CPA are rarely encountered, it should be kept in mind in the list of differential diagnosis, preparing both the surgeon and anesthesiologist for the surgery of a vascular lesion. Specific radiological features, especially an associated developmental venous anomaly could point to the diagnosis.

Multimodal Regional Brain Monitoring of Tissue Ischemia in Severe Cerebral Venous Sinus Thrombosis.

BACKGROUND: Comatose critically ill patients with severe diffuse cerebral venous thrombosis (CVT) are at high risk of secondary hypoxic/ischemic insults, which may considerably worsen neurological recovery. Multimodal brain monitoring (MBM) may therefore improve patient care in this setting, yet no data are available in the literature. METHODS: We report two patients with coma following severe diffuse CVT who underwent emergent invasive MBM with intracranial pressure (ICP), brain tissue oximetry (PbtO2), and cerebral microdialysis (CMD). Therapy of CVT consisted of intravenous unfractionated heparin (UFH), followed by endovascular mechanical thrombectomy (EMT). EMT efficacy was assessed continuously at the bedside using MBM. RESULTS: Despite effective therapeutic UFH (aPTT two times baseline levels in the two subjects), average CMD levels of lactate and glucose in the 6 h prior to EMT displayed evidence of regional brain ischemia. The EMT procedure was associated with a rapid (within 6 h) improvement in both CMD lactate (6.42 ± 0.61 4.89 ± 0.55 mmol/L, p = 0.02) and glucose (0.49 ± 0.17 vs. 0.96 ± 0.32 mmol/L, p = 0.0005). EMT was also associated with a significant increase in PbtO2 (22.9 ± 7.5 vs. 30.1 ± 3.6 mmHg, p = 0.0003) and a decrease in CMD glutamate (12.69 ± 1.06 vs. 5.73 ± 1.76 µmol/L, p = 0.017) and intracranial pressure (ICP) (13 ± 4 vs. 11 ± 4 mmHg (p = 004). Patients did not require surgical decompression, regained consciousness, and were discharged from the hospital with a good neurological outcome (modified Rankin score 3 and 4). CONCLUSIONS: This study illustrates the potential utility of continuous bedside MBM in patients with coma after severe brain injury, irrespective of the primary acute cerebral condition. Despite adequate ICP and PbtO2 control, the presence of CMD signs of regional brain cell ischemia triggered emergent EMT to treat CVT, which was associated with a significant and clinically relevant improvement of intracerebral physiology.