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Objectives: To assess the diagnostic accuracy of nerve thickening on MRI to predict early-stage postlaminar optic nerve invasion (PLONI) in retinoblastoma. Furthermore, this study aimed to incorporate measurements into a multiparametric model for radiological determination of PLONI. Methods: In this retrospective multicenter case–control study, high-spatial-resolution 3D T2-weighted MR images were used to measure the distal optic nerve. Histopathology was the reference standard for PLONI. Two neuroradiologists independently measured the optic nerve width, height, and surface at 0, 3, and 5 mm from the most distal part of the optic nerve. Subsequently, PLONI was scored on contrast-enhanced T1-weighted and 3D T2-weighted images, blinded for clinical data. Optic nerve measurements with the highest diagnostic accuracy for PLONI were incorporated into a prediction model for radiological determination of PLONI. Results: One hundred twenty-four retinoblastoma patients (median age, 22 months [range, 0–113], 58 female) were included, resulting in 25 retinoblastoma eyes with histopathologically proven PLONI and 206 without PLONI. ROC analysis of axial optic nerve width measured at 0 mm yielded the best area under the curve of 0.88 (95% confidence interval: 0.79, 0.96; p < 0.001). The optimal width cutoff was ≥ 2.215 mm, with a sensitivity of 84% (95% CI: 64, 95%) and specificity of 83% (95% CI: 75, 89%) for detecting PLONI. Combining width measurements with the suspicion of PLONI on MRI sequences resulted in a prediction model with an improved sensitivity and specificity of respectively up to 88% and 92%. Conclusion: Postlaminar optic nerve thickening can predict early-stage postlaminar optic nerve invasion in retinoblastoma. Clinical relevance statement: This study provides an additional tool for clinicians to help determine postlaminar optic nerve invasion, which is a risk factor for developing metastatic disease in retinoblastoma patients. Key Points: • The diagnostic accuracy of contrast-enhanced MRI for detecting postlaminar optic nerve invasion is limited in retinoblastoma patients. • Optic nerve thickening can predict postlaminar optic nerve invasion. • A prediction model combining MRI features has a high sensitivity and specificity for detecting postlaminar optic nerve invasion. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the adverse effects of selective intra-arterial chemotherapy (SIAC) on the eyes and optic nerves of retinoblastoma patients using magnetic resonance imaging (MRI). We aim to understand the post-SIAC changes in orbital and ocular structures and evaluate their impact on eye and optic nerve growth. Experienced radiologists analyzed MR images of retinoblastoma eyes treated with SIAC, comparing them to eyes treated with other eye-saving methods and healthy eyes. Results reveal common adverse effects like inflammation and vascular changes, along with significant ocular growth arrest and optic nerve atrophy in eyes treated with SIAC, especially in children treated ≤ 12 months of age. This study underscores the importance of careful consideration when utilizing SIAC, particularly in young patients, due to its potential negative effects on eye and optic nerve development. This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research. [ABSTRACT FROM AUTHOR]

Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1–73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3–9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications. [ABSTRACT FROM AUTHOR]

Objectives: To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. Methods: In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. Results: Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated. Conclusions: A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. Clinical relevance statement: Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. Key Points: • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma. [ABSTRACT FROM AUTHOR]

To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion. A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case–control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls. A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis. In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case–control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons. Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed. The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P < 0.001), and a larger eye size (P = 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16–52) to 89% (95% CI, 72–98). Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes. [ABSTRACT FROM AUTHOR]

Background: Rare mechanisms of stroke (RMS) in acute ischemic stroke (AIS) have rarely been studied applying a systematic approach. Our aim was to define the frequency, etiologies, predictors, and outcomes of RMS in a consecutive series of AIS. Methods: Data from consecutive patients from 2003 to 2016 were derived from the Acute STroke Registry and Analysis of Lausanne (ASTRAL). Frequency of subcategories of RMS was calculated. In a case–control design, RMS were compared to strokes of all other mechanisms. Outcome was assessed with 3-month Rankin-shift and 12-month mortality and recurrence rates. Results: Out of 4154 AISs, 222 (5.3%) were found to have a RMS (42.0% female, median age 66 years). The most frequent RMS etiologies were medical interventions (25.6%), active oncological disease (22.5%), and vasculitis (11.7%). In multivariate analysis, RMS patients were younger, had more preceding and bilateral strokes, and a higher admission temperature. They were associated with less traditional risk factors and more systemic disease (such as AIDS, coagulopathy, and cancer). RMS also had more early ischemic changes on plain CT, less revascularization treatments, and more symptomatic hemorrhagic transformations. They presented significantly higher 3-month disability (Rankin-shift-ORadj 1.74), 12-month recurrence (ORadj 1.99), and mortality rates (ORadj 2.41). Conclusions: RMS occurred in 5.3% of a large population of consecutive AISs and are most frequently related to medical interventions, cancer, and vasculitis. RMS patients have less traditional risk factors but more systemic comorbidities, hemorrhagic transformations, recurrences, and a worse long-term outcome. Identification of RMS has direct implications for early treatment and long-term outcome. [ABSTRACT FROM AUTHOR]

Background: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate lesions on diffusion-weighted imaging (hippocampal punctate diffusion lesion, HPDL). The recent literature suggests that TGA may be triggered by acute neurological conditions.Objective: To study patients with TGA triggered by an acute neurological disease.Methods: We retrospectively reviewed patients from two neurology centres with TGA (with or without HPDL) in whom an acute neurological condition could be identified as trigger. We also performed a systematic review of the literature of this situation using predefined search terms.Results: We identified 38 patients (median age 62 years, 55.3% female): 6 from our centres and 32 from the literature. Acute neurovascular diseases that preceded or were associated with TGA included ischemic and haemorrhagic strokes, convexity subarachnoid haemorrhage, and reversible cerebral vasoconstriction syndrome. As non-vascular acute neurological diseases, we identified migraine and peripheral-origin vertigo. The clinical manifestation of the neurological trigger showed a variable temporal relation with TGA onset; in some cases preceding and in others co-occurring with TGA manifestation. In some cases, presumed neurological triggers were asymptomatic and diagnosed from the neuroimaging done for the TGA.Conclusions: Acute vascular and non-vascular neurological events may trigger TGAs or may occur simultaneously. In the first case, such an acute neurological disease may activate direct pathways within the nervous systems leading to TGA, or alternatively elicit a bodily sympathetic overactivity cascade. In the second case, both neurological events may be the result of a common external stressor. [ABSTRACT FROM AUTHOR]

We present a patient who developed, after an early‐onset, a stable course of spastic paraplegia and ataxia for 4 decades and eventually succumbed to two episodes of postinfectious lactic acidosis. Diagnostic workup including muscle biopsy and postmortem analysis, oxymetric analysis, spectrophotometric enzyme analysis, and MitoExome sequencing revealed a necrotizing leukoencephalomyelopathy due to the so far unreported biallelic variant of the NDUFV1 gene (p.(Pro122Leu)). This case extends our understanding of NDUFV1 variants with a 14‐fold longer lifetime than so far reported cases, and will foster sensitivity toward respiratory chain disease also in adult patients with sudden deteriorating neurological deficits. [ABSTRACT FROM AUTHOR]

Objective: Impact of different MR perfusion software on selection and outcome of patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO) treated by endovascular thrombectomy (EVT) is unclear. We aimed at comparing two commercial MRI software, semi-automated with unadjusted (method A) and adjusted mask (method B), and fully automated (method C) in this setting. Methods: MRI from 144 consecutive AIS patients with anterior circulation LVO was retrospectively analysed. All diffusion- and perfusion-weighted images (DWI-PWI) were post-processed with the three methods using standard thresholds. Concordance for core and hypoperfusion volumes was assessed with Lin's test. Clinical outcome was compared between groups in patients who underwent successful EVT in the early and late time window. Results: Mean core volume was higher and mean hypoperfusion volume was lower in method C than in methods A and B. In the early time window, methods A and B found fewer patients with a mismatch ratio ≤ 1.2 than method C (1/67 [1.5%] vs. 12/67 [17.9%], p = 0.0013). In the late time window, methods A and B found fewer patients with a mismatch ratio < 1.8 than method C (3/46 [6.5%] and 2/46 [4.3%] vs. 18/46 [39.1%], p ≤ 0.0002). More patients with functional independence at 3 months would not have been treated using method C versus methods A and B in the early (p = 0.0063) and late (p ≤ 0.011) time window. Conclusions: MRI software for DWI-PWI analysis may influence patients' selection before EVT and clinical outcome. Key Points: • Method C detects fewer patients with favourable mismatch profile. • Method C might underselect more patients with functional independence at 3 months. • Software used before thrombectomy may influence patients' outcome. [ABSTRACT FROM AUTHOR]

Introduction: Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. Method: We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years followup were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1-73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3-9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Results: Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. Conclusion: For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications. [ABSTRACT FROM AUTHOR]

Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate diffusion-weighted imaging lesions (HPDL). The literature suggests that TGA may present with unusual features. This study analyses atypical clinical and radiological manifestations of patients with TGA and/or HPDL. We retrospectively reviewed patients with atypical clinical or radiological presentations of TGA and/or HPDL in three neurology centers. We also performed a systematic review of literature using predefined search terms. Results were classified as: A) Atypical clinical manifestations of TGA (such as amnesia with additional manifestations, or only non-amnesic manifestations); B) Atypical radiological manifestations of clinically typical TGA. We identified 83 patients: 18 in our centres (median age 63.5 years, 39% female) and 65 in the literature. In group A, 43 patients presented atypical clinical manifestations such as TGA with added transitory cognitive or sensory-motor deficits, seizures, headaches, but also non-amnesic presentations associated with HPDL and incidental HPDL without symptoms. In group B, 40 patients with typical clinical TGA showed extra-hippocampal punctate diffusion lesions (E -HPDL) which disappeared on follow-up imaging. Using clinical and radiological manifestations, we classified these patients into different categories describing a "TGA-PDL spectrum". TGA may have atypical clinical manifestations despite typical neuroimaging and patients with typical TGA may show vanishing extra-hippocampal punctate diffusion lesions. TGA, related clinical manifestations, and vanishing punctate diffusion lesions should be considered part of a larger "TGA-PDL spectrum", allowing for better diagnosis of typical and atypical cases and stimulating further studies. • TGA may occasionally be accompanied by clinical features outside the strict original definition. • In addition to the characteristic HPDL, extra-hippocampal punctate vanishing lesions may be seen in TGA. • We propose a the term "TGA-HPDL spectrum", allowing classification also of atypical clinical and radiological cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Although secondary enucleation (SE) is the treatment of choice for retinoblastoma eyes that did not respond favorably to conservative therapies, clear criteria for its indication are, however, currently missing. In this position paper on behalf of the European Retinoblastoma Group (EURbG), we discuss the available literature on SE, including its influence on metastases rate and survival, and propose guidelines to assist decision-making to interrupt eye-preserving therapies depending on the availabilities of advanced diagnostic and therapeutic modalities. Absolute indications to SE may be restricted to eyes with refractory tumor activity resisting all salvage treatments or eyes under apparent tumor control but no visual potential and irreducible complications. In contrast, eyes with an obscured optic nerve head and/or ocular complications amenable to specific surgical or medical management can be considered relative indications, provided that appropriate follow-up can be implemented and that parents are fully aware of a residual risk. Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future. [ABSTRACT FROM AUTHOR]