Outcomes of Patients with Non-Small Cell Lung Cancer and Brain Metastases Treated with the Upfront Single Agent Pembrolizumab: A Retrospective and Multicentric Study of the ESCKEYP GFPC Cohort.

Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Little is known about immune checkpoint inhibitor activity in the central nervous system, especially in patients receiving monotherapy for tumors with a tumor proportion score (TPS) ≥ 50%. This noninterventional, retrospective, multicenter study, conducted with the GFPC, included treatment-naïve patients strongly positive for PD-L1 (TPS ≥ 50%) with BM receiving first-line single-agent pembrolizumab treatment between May 2017 and November 2019. The primary endpoints were centrally reviewed intracranial overall response rates (ORRs), centrally reviewed intracranial progression-free survival (cPFS), extracranial PFS, and overall survival were secondary endpoints. Forty-three patients from five centers were included. Surgical or local radiation therapy was administered to 31 (72%) patients, mostly before initiating ICI therapy (25/31). Among 38/43 (88.4%) evaluable patients, the intracranial ORR was 73%. The median PFS was 8.3 months. The cerebral and extracerebral median PFS times were 9.2 and 5.3 months, respectively. The median OS was 25.5 months. According to multivariate analysis, BM surgery before ICI therapy was the only factor significantly associated with both improved PFS (HR = 0.44) and OS (HR = 0.45). This study revealed the feasibility and outcome of front-line pembrolizumab treatment in this population with BM.

Is the OCT a predictive tool to assess visual impairment in optic chiasm compressing syndrome in pituitary macroadenoma? A prospective longitudinal study.

Visual dysfunction is a prevalent symptom in patients with non-functioning pituitary macroadenoma (NFPM); the role of OCT in such patients has not been yet determined. This is a prospective longitudinal observational study over a period of 6 years, on 20 patients presenting a radiological compression of the optic chiasma without visual acuity (VA) and visual field (VF) disturbances. The primary endpoint was to evaluate the impact of NFPA on neuro-axonal loss by measuring RNFL thickness using OCT at inclusion (T0), 12 months (T1), 24 months (T2), and 36 months (T3), respectively. The secondary endpoint was to monitor the evolution of OCT over time and assess any relationship between the degree of OCT alteration and the degree of radiological and clinical optic chiasm compression syndrome. Among the 20 patients included, eight (40%) showed an altered RNFL-OCT at diagnosis, while the remaining 12 (60%) showed a normal pattern. During a mean ophthalmologic follow-up of 60 months, 4 patients (20%) presented an asymptomatic reduction of RNFL-OCT thickness although all 20 had a VA/VF stable. To our knowledge, this study represents the first attempt to longitudinally evaluate the natural history and evolution of RNFL-OCT in patients with radiologically asymptomatic chiasmatic compression syndrome. The results do not clearly demonstrate the role of the OCT as an early prognostic factor for visual dysfunction.

Approaching Intradural Lesions of the Anterior Foramen Magnum and Craniocervical Junction: Anatomical Comparison of the Open Posterolateral and Anterior Extended Endonasal Endoscopic Approaches.

BACKGROUND: Lesions of the foramen magnum (FM) and craniocervical junction area are traditionally managed surgically through anterior, anterolateral, and posterolateral skull-base approaches. This anatomical study aimed to compare the usefulness of a modified extended endoscopic approach, the so-called far-medial endonasal approach (FMEA), versus the traditional posterolateral far-lateral approach (FLA). METHODS: Ten fixed silicon-injected heads specimens were used in the Skull Base ENT-Neurosurgery Laboratory of the University Hospital of Strasbourg, France. A total of 20 FLAs and 10 FMEAs were realized. A high-resolution computed tomography scan was performed for quantitative analysis of the different approaches. The analysis aimed to estimate the extent of surgical exposure and freedom of movement (maneuverability) through the operating channel using a polygonal surface model to obtain a morphometric estimation of the area of interest (surface and volume) on postdissection computed tomography scans using Slicer 3D software. RESULTS: FMEA allows for a more direct route to the anterior FM, with wider brainstem exposure compared with the FLA and an excellent visualization of all anterior midline structures. The limitations of the FMEA include the deep and narrow surgical corridor and difficulty in reaching lesions located laterally over the jugular foramen and hypoglossal canal. CONCLUSIONS: The FMEA and FLA are both effective surgical routes to reach FM and craniocervical junction lesions. Modern skull base surgeons should have a good command of both because they appear complementary. This anatomical study provides the tools for comprehensive preoperative evaluations and selection of the most appropriate surgical approach.

Pituitary Abscess: A Challenging Preoperative Diagnosis-A Multicenter Study.

Background and Objectives: Pituitary abscess (PA) is a rare occurrence, representing less than 1% of pituitary lesions, and is defined by the presence of an infected purulent collection within the sella turcica. Pas can be classified as either primary, when the underlying pituitary is normal prior to infection, or secondary, when there is associated a pre-existing sellar pathology (i.e., pituitary adenoma, Rathke's cleft cysts, or craniopharyngioma), with or without a recent history of surgery. Preoperative diagnosis, owing to both non-specific symptoms and imaging features, remains challenging. Treatment options include endonasal trans-sphenoidal pus evacuation, as well as culture and tailored antibiotic therapy. Methods: A retrospective multicenter study, conducted on a prospectively built database over a 20-year period, identified a large series of 84 patients harboring primary sellar abscess. The study aimed to identify crucial clinical and imaging features in order to accelerate appropriate management. Results: The most common clinical presentation was a symptom triad consisting of various degrees of asthenia (75%), visual impairment (71%), and headache (50%). Diagnosis was achieved in 95% of cases peri- or postoperatively. Functional recovery was good for visual disturbances and headache. Pituitary function recovery remained very poor (23%), whereas the preoperative diagnosis represented a protective factor. Conclusions: In light of the high prevalence of pituitary dysfunction following the management of PAs, early diagnosis and treatment might represent a crucial issue. Currently, there are no standard investigations to establish a conclusive preoperative diagnosis; however, new, emerging imaging methods, in particular nuclear imaging modalities, represent a very promising tool, whose potential warrants further investigations.

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

Endoscopic-enhanced supra-cerebellar trans-tentorial (SCTT) approach to temporo-mesial region: a multicenter study.

Surgical access to the temporo-mesial area may be achieved by several routes such as the sub-temporal, the temporal trans-ventricular, the pterional/trans-sylvian, and the occipital interhemispheric approaches; nonetheless, none of them has shown to be superior to the others. The supra-cerebellar trans-tentorial approach allows a great exposure of the middle and posterior temporo-mesial region, while avoiding temporal lobe retraction. A prospective multicenter study was designed to collect data on patients undergoing endoscopic-enhanced SCTT approach to excise left temporo-mesial lesions. The study involved 5 different neurosurgical European centers and ran from 2015 to 2020. All patients had preoperative as well as postoperative brain MRI and ophthalmology evaluation. A total of 30 patients were included in this study, the mean follow-up was 44 months (range 18 to 84 months), male/female ratio was 16/14, and mean age was 39 years. A gross total resection was achieved in 29/30 (96.7%) cases. All surgical procedures were uneventful, without transient or permanent neurological deficits thanks to the preservation of the posterior cerebral artery. The endoscopic-enhanced SCTT approach provides satisfactory exposure to the left temporo-mesial region. Its minimally invasive nature helps minimize the surgical risks related to vascular and white tract manipulation, which represent known limitations of open microsurgical as well as other approaches.

Efficacy of endoscopic management of primary central nervous system lymphoma: a multicentric study and literature review.

INTRODUCTION: To date, confined intra-ventricular localization of primary central nervous system lymphoma (PCNSL) has been usually managed with open surgical resection and/or stereotactic biopsy; nonetheless, the endoscopic approach to such localization can provide many advantages over standard microsurgery and/or stereotactic biopsy. Here we present our experience in managing such a rare pathology through the endoscopic approach. METHOD: In order to gather more information about such a rare pathology, a retrospective multicentric study on a prospectively built database has been performed during a 5 year period. Ten different European centers have been involved. RESULTS: A total of 60 patients, 25 women and 35 men, have been enrolled in the study. The mean age was 65.3 years. The mean lesion size was 40.3 mm. Among all selected patients, 40 (66.6%) had superficial lesions within the ventricle, whereas the remaining 20 (33.4%) had lesions involving/extending to deeper structures. All surgical procedures were uneventful and ETV was deemed necessary only in 20/60 cases. CONCLUSION: In our experience, endoscopic management of intraventricular PCNSL is an effective option. It should be considered after a careful examination of neurological and immunological status, alternative options for diagnostic sampling, location of the lesion, and presence or absence of hydrocephalus. Endoscopic management could be considered as a safe and minimally invasive option to obtain: (a) a biopsy sample of the lesion for further diagnostic workup, (b) CSF diversion through third ventriculostomy or VP shunt for the management of hydrocephalus, and (c) insertion of ventricular access devices for long term medical management and whenever necessary as a rescue option for ventricular tap.

MRI dedicated to the emergency department for diplopia or dizziness: a cost-effectiveness analysis.

OBJECTIVES: The purpose of this study was to compare the costs and organizational benefits of diagnostic workup without and with MRI dedicated to the ED. METHODS: We conducted a prospective observational uncontrolled before-after study in one ED of a university hospital in France from July 1, 2018, and January 3, 2020. We included all consecutive patients presenting with dizziness or diplopia. The main outcomes were the clinical decision time of ED physicians and the total costs for each strategy. Outcomes were compared using propensity score with inverse probability weighting in the 2 arms and an incremental cost-effectiveness ratio (ICER) was calculated. RESULTS: Among the 199 patients during the "before" period (average age: 60.4 years ± 17.6): 112 men (57%), and 181 during the "after" period (average age, 54.8 years ± 18.5): 107 men (59%), the average costs were €2701 (95% CI 1918; 3704) and €2389 (95% CI: €1627; 3280) per patient, respectively. The average time to clinical decision was 9.8 h (95% CI: 8.9 10.7) in the group "before" and 7.7 h (95% CI: 7.1; 8.4) in the group "after" (ICER: €151 saved for a reduction of 1 h in clinical decision time). The probabilistic sensitivity analysis estimated a 71% chance that the MRI dedicated to ED was dominant (less costly and more effective). CONCLUSION: Easy access to MRI in the ED for posterior circulation stroke-like symptoms must be considered a relevant approach to help physicians for an appropriate and rapid diagnostic with reduction of costs. TRIAL REGISTRATION: NCT03660852 KEY POINTS: • A dedicated MRI in the ED for diplopia or dizziness may be considered an efficient strategy improving diagnostic performance, reducing physicians' decision time, and decreasing hospital costs. • This strategy supports clinical decision-making with early treatment and management of patients with posterior circulation-like symptoms in the ED. • There is 71% chance that the MRI dedicated to ED was dominant (less costly and more effective) compared with a strategy without dedicated MRI.

Evolution of Neuroimaging Findings in Severe COVID-19 Patients with Initial Neurological Impairment: An Observational Study.

BACKGROUND AND OBJECTIVES: Cerebral complications related to the COVID-19 were documented by brain MRIs during the acute phase. The purpose of the present study was to describe the evolution of these neuroimaging findings (MRI and FDG-PET/CT) and describe the neurocognitive outcomes of these patients. METHODS: During the first wave of the COVID-19 outbreak between 1 March and 31 May 2020, 112 consecutive COVID-19 patients with neurologic manifestations underwent a brain MRI at Strasbourg University hospitals. After recovery, during follow-up, of these 112 patients, 31 (initially hospitalized in intensive care units) underwent additional imaging studies (at least one brain MRI). RESULTS: Twenty-three men (74%) and eight women (26%) with a mean age of 61 years (range: 18-79) were included. Leptomeningeal enhancement, diffuse brain microhemorrhages, acute ischemic strokes, suspicion of cerebral vasculitis, and acute inflammatory demyelinating lesions were described on the initial brain MRIs. During follow-up, the evolution of the leptomeningeal enhancement was discordant, and the cerebral microhemorrhages were stable. We observed normalization of the vessel walls in all patients suspected of cerebral vasculitis. Four patients (13%) demonstrated new complications during follow-up (ischemic strokes, hypoglossal neuritis, marked increase in the white matter FLAIR hyperintensities with presumed vascular origin, and one suspected case of cerebral vasculitis). Concerning the grey matter volumetry, we observed a loss of volume of 3.2% during an average period of approximately five months. During follow-up, the more frequent FDG-PET/CT findings were hypometabolism in temporal and insular regions. CONCLUSION: A minority of initially severe COVID-19 patients demonstrated new complications on their brain MRIs during follow-up after recovery.

Evaluation of neuroradiology emergency MRI interpretations: low discrepancy rates between on-call radiology residents' preliminary interpretations and neuroradiologists' final reports.

OBJECTIVES: To evaluate the performance of on-call radiology residents in interpreting alone brain and spine MRI studies performed after hours, to describe their mistakes, and to identify influencing factors that increased the occurrence of errors. METHODS: A total of 328 MRI examinations performed during a 13-month period (from December 1, 2019, to January 1, 2021) were prospectively included. Discrepancies between the preliminary interpretation of on-call radiology residents and the final reports of attending neuroradiologists were noted and classified according to a three-level score: level 1 (perfect interpretation or minor correction), level 2 (important correction without immediate change in patient management), or level 3 (major correction with immediate change in patient management). Categorical data were compared using Fisher's exact test. RESULTS: The overall discrepancy rate (level-2 and level-3 errors) was 16%; the rate of major discrepancies (only level-3 errors) was 5.5%. The major-discrepancy rate of second-year residents, when compared with that of senior residents, was significantly higher (p = 0.02). Almost all of the level-3 errors concerned cerebrovascular pathology. The most common level-2 errors involved undescribed aneurysms. We found no significant difference in the major-discrepancy rate regarding time since the beginning of the shift. CONCLUSIONS: The great majority of examinations were correctly interpreted. The rate of major discrepancies in our study was comparable to the data in the literature, and there was no adverse clinical outcome. The level of residency has an effect on the rate of serious errors in residents' reports. KEY POINTS: • The rate of major discrepancies between preliminary MRI interpretations by on-call radiology residents and final reports by attending neuroradiologists is low, and comparable to discrepancy rates reported for head CT interpretations. • The youngest residents made significantly more serious errors when compared to senior residents. • There was no adverse clinical outcome in patient morbidity as a result of an initial misdiagnosis.

Immune-related aseptic meningitis and strategies to manage immune checkpoint inhibitor therapy: a systematic review.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) can induce adverse neurological effects. Due to its rarity as an adverse effect, meningitis has been poorly described. Therefore, meningitis diagnosis and management can be challenging for specialists. Moreover, meningitis can be an obstacle to resuming immunotherapy. Given the lack of alternatives, the possibility of reintroducing immunotherapy should be discussed on an individual basis. Here, we present a comprehensive systematic review of meningitis related to ICIs. REVIEW: We performed a search for articles regarding immune-related meningitis published in PubMed up to November 2021 with the MeSH terms "meningitis" and "immune checkpoint" using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized the studies not only by category but also based on whether it was a primary article or case report to provide a systematic overview of the subject. We reviewed a total of 38 studies and herein report the clinical experiences, pharmacovigilance data and group knowledge from these studies. CONCLUSION: This review summarizes the existing information on immune-related meningitis and the possibility of reintroducing immunotherapy after the development of central neurological side effects. To the best of our knowledge, there is little information in the literature to guide clinicians on decisions regarding whether immunotherapy should be continued after a neurological adverse event occurs, especially meningeal events. This review emphasizes the necessity of systematic examinations, steroid treatment (as a cornerstone of management) and the need for further exploratory studies to obtain a clearer understanding of how to better manage patients who experience these side effects. The findings summarized in this review can help provide guidance to practitioners who face this clinical situation.

Immune-Related Cerebellar Ataxia: A Rare Adverse Effect of Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitors (ICIs) have led to a revolution in cancer management, mainly due to lasting long-term durable responses in a subset of patients with metastatic solid tumours (Gettinger et al. in JCO 36(17):1675-1684, 2018). As immunotherapy is gradually being applied for the treatment of a large range of solid tumours, the incidence of neurological immune-related adverse events (irAEs) has increased (2). Neurologic toxicities that result in high morbidity rates and even mortality have emerged as serious complications of ICIs (Johnson et al. in J Immuno Cancer 7(1):134, 2019; Wang et al. in JAMA Oncol 4(12):1721, 2018). Small-cell lung cancer (SCLC) is common cause of neurologic paraneoplastic syndrome (Sebastian et al. in J Thorac Oncol 14(11):1878-1880, 2019). Nevertheless, the distinction between neurologic iRAEs and paraneoplastic neurological syndromes (PNSs) in patients with SCLC treated by ICIs remains challenging (Williams et al. JAMA Neurol 73(8):928, 2016). As immunotherapy is gradually being applied for the treatment of a large range of solid tumours, the incidence of neurological autoimmune adverse events has increased. Neurologic toxicities that result in high morbidity rates and even mortality have emerged as serious complications of ICIs and have yet to be fully understood. We report a case of an immune induced cerebellar ataxia in a 47 year-old small-cell neuroendocrine carcinoma patient undergoing checkpoint blockade by atezolizumab, a programmed cell death-1 ligand (PDL-1) inhibitor. After 4 cycles of immunotherapy, the patient presented with kinetic and static cerebellar syndrome leading to the diagnosis of TRIM9-Abs ICI-related cerebellar irAE. Therapeutic management was discussed in multidisciplinary meetings in the lack of therapeutic guidelines. There was no clinical improvement. Because of high morbidity and no treatment evidence, neurologic symptoms developing under ICI require early diagnosis and may indicate the need for definitive treatment discontinuation.

Odontoid Type II fractures in elderly: what are the real management goals and how to best achieve them? A multicenter European study on functional outcome.

Odontoid fractures constitute the most common cervical fractures in elderly. External immobilization is the treatment of choice for Type I and III; there is still no wide consensus about the best management of Type II fractures. Observational multicenter study was conducted on a prospectively built database on elderly patients (> 75 years) with Type II odontoid fracture managed conservatively during the last 10 years. All patients underwent CT scan on admission and at 3 months; if indicated, selected patient had CT scan at 6 and 12 months. All patients were clinically evaluated by Neck Disability Index (NDI), Charlson Comorbidity Index (CCI), and American Society of Anaesthesiologists classification (ASA) on admission; NDI was assessed also at 6 weeks, 3, 6, 12, and 24 months; furthermore, a quality of life (QoL) assessment with the SF-12 form was performed at 3 and 12 months. Among the 260 patients enrolled, 177 (68%) were women and 83 (32%) men, with a median age of 83 years. Patients were followed up for a minimum of 24 months: 247 (95%) showed an excellent functional outcome within 6 weeks, among them 117 (45%) showed a good bony healing, whereas 130 (50%) healed in pseudo-arthrosis. The residual 5% were still variably symptomatic at 12 weeks; however, only 5 out of 13 (2% of the total cohort) required delayed surgery. This study showed that a conservative approach to odontoid Type II fracture in elderly is an effective and valid option, resulting in an excellent functional outcome (regardless of bony fusion) in the majority of cases. Failure of conservative treatment can be safely addressed with surgical fixation at a later stage.

Does interventional MRI-guided brain cryotherapy cause a blood-brain barrier disruption? Radiological analysis and perspectives.

Glioblastoma is the most common primary malignant brain tumor with an incidence of 5/100,000 inhabitants/year and a 5-year survival rate of 6.8%. Despite recent advances in the molecular biology understanding of glioblastoma, CNS chemotherapy remains challenging because of the impermeable blood-brain barrier (BBB). Interventional MRI-guided brain cryotherapy (IMRgC) is technique that creates a tissue lesion by making a severe targeted hypothermia and possibly a BBB disruption. This study goal was to analyze the effect of IMRgC on human BBB glioblastoma through its gadolinium enhancing features. All patients harboring a local glioblastoma recurrence and meeting all the inclusion criteria were consecutively included into this retrospective study during a 2-year period. The primary endpoint was to analyze the modification of the gadolinium enhancement on MRI T1 sequences using MR perfusion weighted images during follow-up. The secondary endpoint was to assess any ischemic/hemorrhagic complication following cryotherapy procedure using diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), or fluid-attenuated inversion recovery (FLAIR). Among the 6 patients studied, all (100%) showed a BBB disruption on the cryotherapy site through the analysis of the perfusion weighted images with an average delay of 2.83 months following the procedure. The gadolinium enhancement located around the cavity then spontaneously decreased in 4/6 patients (67%). No ischemic or hemorrhagic complication was recorded. This study confirms the IMRgC capacity to disrupt BBB as already suggested by the literature. IMRgC might represent a new option in the management of GBM allowing the combined effect of direct cryoablation and enhanced chemotherapy.

Primary Endoscopic Endonasal Management of Giant Pituitary Adenomas: Outcome and Pitfalls from a Large Prospective Multicenter Experience.

PURPOSE: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). METHODS: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic features, visual and hormonal outcomes, extent of resection (EoR), complications and recurrence rates were recorded and analyzed. RESULTS: Of 1169 patients treated for pituitary adenoma, 96 (8.2%) had GPAs. Seventy-eight (81.2%) patients had visual impairment, 12 (12.5%) had headaches, 3 (3.1%) had drowsiness due to hydrocephalus, and 53 (55.2%) had anterior pituitary insufficiency. EoR was gross or near-total in 46 (47.9%) and subtotal in 50 (52.1%) patients. Incomplete resection was associated with lateral suprasellar, intraventricular and/or cavernous sinus extension and with firm/fibrous consistence. At the last follow-up, all but one patient (77, 98.7%) with visual deficits improved. Headache improved in 8 (88.9%) and anterior pituitary function recovered in 27 (50.9%) patients. Recurrence rate was 16.7%, with 32 months mean recurrence-free survival. CONCLUSIONS: EEA-TTP is a valid option for GPAs and seems to provide better outcomes, lower rate of complications and higher EoR compared to one- or multi-stage microscopic, non-extended endoscopic transsphenoidal, and transcranial resections.

Endoscopic Transorbital Approaches to Anterior and Middle Cranial Fossa: Exploring the Potentialities of a Modified Lateral Retrocanthal Approach.

BACKGROUND: Among the new perspectives to revolutionize skull base surgery, there are the transorbital neuroendoscopic (TONES) approaches to reach the anterior and middle cranial fossa (ACF and MCF). We conceived to explore the potentialities of a modified superiorly and medially extended lateral retrocanthal (LRC) approach. METHODS: Six head specimens were dissected. Applying the established conic model and the key surgical landmark of sphenofrontal suture, we tested the feasibility of a modified LRC to reach ACF and MCF; computed tomography (CT) scans were performed before and after dissection to obtain a morphometric analysis of the surgical corridors using a polygonal surfaces model. RESULTS: Through our anatomical study, we were able to identify and explore 3 different surgical corridors to reach the ACF and MCF: the superomedial, the superolateral, and the inferolateral. The superomedial corridor appeared most suitable to reach the medial part of the ACF and the optic-carotid region, whereas through the superolateral and inferolateral corridors it was possible to reach and explore the lateral part of ACF and MCF. The mean volumes of the 3 surgical corridors calculated on post-dissection CT scans were: 12.72 ± 1.99, 5.69 ± 0.34, and 6.24 ± 0.47 cm3, respectively. CONCLUSIONS: The development of TONES approaches has not replaced the traditional open or endoscopic approach; nonetheless, identification of surgical corridors and the possibility to combine them represent a major breakthrough. Clinical studies are necessary to demonstrate their validity and test the effectiveness, safety, and reproducibility of TONES approaches in managing lesions harboring in the ACF and MCF.

Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML.

OBJECTIVES: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. MATERIALS AND METHODS: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. RESULTS: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. CONCLUSION: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. KEY POINTS: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution "the milky way," and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.

Association of cerebral microbleeds with cerebrospinal fluid Alzheimer-biomarkers and clinical symptoms in early dementia with Lewy bodies.

OBJECTIVES: To determine the prevalence, localization and associations of cerebral microbleeds (CMB) in dementia with Lewy bodies (DLB) with its core clinical symptoms and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). We hypothesize DLB patients with CMB have increased amyloid burden compared to those without CMB, which could also translate into clinical differences. METHODS: Retrospective cross-sectional analysis from the AlphaLewyMA study (https://clinicaltrials.gov/ct2/show/NCT01876459). Patients underwent a standardized protocol of brain MRI including 3D T1, 3D FLAIR and T2* sequences, and CSF analysis of AD biomarkers. CMB and white matter hyperintensities (WMHs) were visually assessed in prodromal and mild demented (DLB, N = 91) and AD (AD, N = 67) patients. RESULTS: CMB prevalence did not differ among DLB and AD (24.2% vs. 37.3%; p = 0.081). CMB were mainly distributed in lobar topographies in both DLB (74%) and AD (89%). CMB in DLB was not associated with global cognitive performance, executive functioning, speed of information processing, or AD CSF biomarkers. Similarly, there was no difference regarding specific clinical symptoms: fluctuations, psychotic phenomena, sleep behavior disorder and Parkinsonism between DLB patients with and without CMB. AD patients with CMB had increased burden of WMH compared to those without (2.1 ± 0.86 vs. 1.4 ± 0.89; p = 0.005), according to Fazekas scale, whereas no significant difference was observed in DLB patients (1.68 ± 0.95 vs. 1.42 ± 0.91; p = 0.25). CONCLUSION: CMB were equally prevalent with similar topographic distribution in both DLB and AD patients. CMB was not associated with CSF AD biomarkers or core clinical symptoms in DLB.

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

OBJECTIVE: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations. METHODS: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI. RESULTS: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome (p = 0.006) and more frequently had corticospinal tract signs (p = 0.02). Patients with encephalitis were younger (p = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p = 0.009). CONCLUSIONS: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF. CLINICALTRIALSGOV IDENTIFIER: NCT04368390.

Coronavirus Disease 2019: Associated Multiple Organ Damage.

A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2.