Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = -0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

A Prospective Observational Study of Posterior Tibial Nerve Stimulation in Multiple Sclerosis.

INTRODUCTION AND HYPOTHESIS: The objective was to examine the outcomes of posterior tibial nerve stimulation (PTNS) on bladder, bowel, and sexual health-related quality of life among a cohort of patients with multiple sclerosis (MS) with refractory lower urinary tract symptoms (LUTS). METHODS: Patients with MS and refractory LUTS were recruited for a prospective, observational study using PTNS to treat their symptoms. Patients underwent 12 weekly 30-min PTNS sessions and bladder, bowel, and sexual symptoms were evaluated at baseline, 3, 12, and 24 months with voiding diaries, visual analog scales (VAS), and validated patient-reported questionnaires, including the American Urological Association Symptom Score (AUA-SS), Neurogenic Bladder Symptom Score (NBSS), Michigan Incontinence Symptom Index (M-ISI), Health Status Questionnaire, Sexual Satisfaction Scale, and Bowel Control Scale. RESULTS: A total of 23 patients were recruited: 18 started PTNS and 14 completed 3 months of PTNS. Of the 18 who started PTNS, the mean age was 52 years (SD 12), 61% were female, 83% were white, and most patients had relapsing remitting (39%) MS. Baseline (n=18) and 3-month voiding (n=11) outcomes showed no significant change in number of voids or incontinence episodes. The median VAS symptom improvement was 49 (IQR 26.5, 26) and 9 (53%) patients elected for monthly maintenance PTNS. On paired analysis, there was a significant improvement in median change in NBSS, AUA-SS, and M-ISI. There was no significant change in bowel or sexual dysfunction. CONCLUSIONS: This prospective, observational study of PTNS in patients with MS with refractory LUTS shows improvement in patient-reported bladder outcomes, but not in number of voids per day or bowel or bladder function.

A Teenage Boy With a Radiation-Induced High-Grade Astrocytoma.

ABSTRACT: A 12-year-old boy developed acute headache and vomiting. MRI brain showed a partially cystic suprasellar mass. He underwent cyst fenestration, but the cyst regrew, so he underwent transcranial subtotal resection of the mass. The pathologic diagnosis was adamantinomatous craniopharyngioma. Residual tumor was treated with proton beam radiation therapy, and panhypopituitarism was treated with hormone replacement therapy, including growth hormone. Serial brain MRI scans over several years showed no evidence of tumor recurrence. But at four years after radiation, surveillance MRI showed a new focus of nonenhancing FLAIR hyperintensity in the left basal ganglia attributed to gliosis caused by radiotherapy. Seven months later, he developed progressive right hemiparesis, expressive aphasia, and blurred vision, prompting reevaluation. MRI brain showed new enhancing and T2/FLAIR hyperintense lesions in the midbrain, basal ganglia, thalamus, anterior temporal lobe, and optic tract. The abnormal regions showed low diffusivity and relatively high regional blood flow. Stereotactic biopsy disclosed a WHO Grade 4 astrocytoma, likely radiation-induced. A germline ataxia telangiectasia mutation was found in the tumor tissue. The risk of radiation-induced pediatric brain malignancies is low but may have been increased by the mutation.

Dynamic susceptibility contrast-MRI parameters, ADC values, and the T2-FLAIR mismatch sign are useful to differentiate between H3-mutant and H3-wild-type high-grade midline glioma.

OBJECTIVES: Diffuse midline gliomas, H3K27-altered (DMG-A), are malignant gliomas with an unfavorable prognosis. Knowledge of dynamic susceptibility contrast (DSC) MRI findings and imaging differences with high-grade midline glioma without H3K27 alteration (DMG-W) has been limited. We compared the DSC, ADC, and conventional MRI findings between DMG-A and DMG-W. METHODS: In this single institutional retrospective study, the electronic database of our hospital between June 2015 and May 2021 was searched. Twenty and 17 patients with DMG-A (median, 13 years; range, 3-52 years; 11 females) and DMG-W (median, 40 years; 7-73 years; 9 females), respectively, were found. Normalized relative cerebral blood flow (nrCBF) and normalized corrected relative cerebral blood volume (ncrCBV); normalized maximum, mean, and minimum ADC values; and the prevalence of T2-FLAIR mismatch sign were compared between the two groups using Mann-Whitney U tests and Fisher's exact test. RESULTS: The nrCBF and ncrCBV were significantly lower in DMG-A compared with DMG-W (nrCBF: median 0.88 [range, 0.19-2.67] vs. 1.47 [range, 0.57-4.90] (p < 0.001); ncrCBV: 1.17 [0.20-2.67] vs. 1.56 [0.60-4.03] (p = 0.008)). Normalized maximum ADC (nADCmax) was significantly higher in DMG-A (median 2.37 [1.25-3.98] vs. 1.95 [1.23-2.77], p = 0.02). T2-FLAIR mismatch sign was significantly more common in DMG-A (11/20 (55.0%) vs. 1/17 (5.9%), p = 0.0017). When at least two of nrCBF < 1.11, nADCmax ≥ 2.48, and T2-FLAIR mismatch sign were positive, the diagnostic performance was the highest with accuracy of 0.81. CONCLUSION: DSC-MRI parameters, ADC values, and the T2-FLAIR mismatch sign are useful to differentiate between DMG-A and DMG-W. KEY POINTS: • Diffuse midline glioma, H3K27-altered (DMG-A), showed a significantly lower normalized relative cerebral blood flow and volume compared with H3K27-wild-type counterparts (DMG-W). • T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was significantly more frequent in DMG-A compared to DMG-W. • Indicators that combined DSC parameters, ADC values, and T2-FLAIR mismatch sign, with or without age, are useful to distinguish the two tumors.

Major Changes in 2021 World Health Organization Classification of Central Nervous System Tumors.

The World Health Organization (WHO) published the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) in 2021, as an update of the WHO central nervous system (CNS) classification system published in 2016. WHO CNS5 was drafted on the basis of recommendations from the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and expounds the classification scheme of the previous edition, which emphasized the importance of genetic and molecular changes in the characteristics of CNS tumors. Multiple newly recognized tumor types, including those for which there is limited knowledge regarding neuroimaging features, are detailed in WHO CNS5. The authors describe the major changes introduced in WHO CNS5, including revisions to tumor nomenclature. For example, WHO grade IV tumors in the fourth edition are equivalent to CNS WHO grade 4 tumors in the fifth edition, and diffuse midline glioma, H3 K27M-mutant, is equivalent to midline glioma, H3 K27-altered. With regard to tumor typing, isocitrate dehydrogenase (IDH)-mutant glioblastoma has been modified to IDH-mutant astrocytoma. In tumor grading, IDH-mutant astrocytomas are now graded according to the presence or absence of homozygous CDKN2A/B deletion. Moreover, the molecular mechanisms of tumorigenesis, as well as the clinical characteristics and imaging features of the tumor types newly recognized in WHO CNS5, are summarized. Given that WHO CNS5 has become the foundation for daily practice, radiologists need to be familiar with this new edition of the WHO CNS tumor classification system. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. ©RSNA, 2022.

Central Nervous System Systemic Lupus Erythematosus: Pathophysiologic, Clinical, and Imaging Features.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiple immunologic abnormalities and has the potential to involve the central nervous system (CNS). The prevalence of SLE seems to be growing, possibly because of earlier diagnosis and improved survival; however, the associated mortality is still high. The mortality is associated with disease-related risk factors such as lupus disease activity, young age, and organ damage or with antiphospholipid syndrome (APS). Neuropsychiatric SLE (NPSLE), which is caused by SLE-related CNS involvement, comprises a broad range of neurologic and psychiatric manifestations with varying severity, which can make this disease indistinguishable from other conditions that are unrelated to SLE. No unifying pathophysiology has been found in the etiology of NPSLE, suggesting that this condition has multiple contributors such as various immune effectors and the brain-intrinsic neuroimmune interfaces that are breached by the immune effectors. The postulated neuroimmune interfaces include the blood-brain barrier, blood-cerebrospinal fluid barrier, meningeal barrier, and glymphatic system. On the basis of the immunologic, pathologic, and imaging features of NPSLE, the underlying pathophysiology can be classified as vasculitis and vasculopathy, APS, demyelinating syndrome, or autoimmune antibody-mediated encephalitis. Each pathophysiology has different imaging characteristics, although the imaging and pathophysiologic features may overlap. Moreover, there are complications due to the immunocompromised status caused by SLE per se or by SLE treatment. Radiologists and clinicians should become familiar with the underlying mechanisms, radiologic findings, and complications of NPSLE, as this information may aid in the diagnosis and treatment of NPSLE. Online supplemental material is available for this article. ©RSNA, 2022.

Neuroradiological features of the polymorphous low-grade neuroepithelial tumor of the young: five new cases with a systematic review of the literature.

PURPOSE: Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) is a newly recognized brain tumor with genetic abnormalities frequently involving either BRAF or FGFR2/FGFR3. There are few publications available about the neuroradiological features of PLNTY. In this systematic review, we assessed the demographic, clinical, and neuroradiological features of PLNTY. METHODS: Literature data were extracted from database searches in MEDLINE and SCOPUS databases up to June 10, 2021. Studies reporting on pathologically proven PLNTY with neuroradiological findings were included. After reviewing 103 abstracts, 9 articles encompassing 19 cases met the inclusion criteria. We also added five patients from our hospital. The correlations between the presence of "transmantle-like sign" and the following three factors: duration of seizures; tumor size; and pathologically proven cortical dysplasia, were examined. RESULTS: The median patient age was 15.5 years (range, 5-57 years), and 15/24 (62.5%) were female. All tumors were localized supratentorialy. The main radiological features included cortical or subcortical masses (95.8%) in the temporal lobe (66.7%), calcification (83.3%), well-defined margins (72.7%), solid and cystic components (66.6%), and T2-weighted imaging (T2WI) hyperintensity (50.0%). The duration of seizure was significantly longer (positive vs. negative (median [range]), 24 months [6 - 96 months] vs. 5 months [1 - 12 months], p = 0.042), and the presence of the cortical dysplasia was significantly more frequent (3/8 vs 0/16, p = 0.042) in the patients with transmantle-like sign. CONCLUSION: PLNTY typically represents a calcified, well-defined mass in the supratentorial cortical or subcortical regions. The radiological findings defined here could facilitate the diagnosis of PLNTY.

A Review of Clinical and Imaging Findings in Tumefactive Demyelination.

OBJECTIVE. Tumefactive demyelination mimics primary brain neoplasms on imaging, often necessitating brain biopsy. This article reviews the literature for the clinical and radiologic findings of tumefactive demyelination in various disease processes to facilitate identification of tumefactive demyelination on imaging. CONCLUSION. Both clinical and radiologic findings must be integrated to distinguish tumefactive demyelinating lesions from similarly appearing lesions on imaging. Further research on the immunopathogenesis of tumefactive demyelination and associated conditions will elucidate their interrelationship.

Atypical imaging findings of presumed stroke-like migraine attacks after radiation therapy syndrome in the brainstem.

The authors present an atypical case of presumed stroke-like migraine attacks after radiation therapy (SMART) syndrome in the brainstem. A 29-year-old male, who had been treated with resection and subsequent craniospinal radiation for posterior fossa medulloblastoma 21 years before, presented with subacute progressive left hemiparesis evolving over 4 days. Hematological findings, cerebrospinal fluid (CSF), and electroencephalogram (EEG) were unremarkable. Magnetic resonance imaging (MRI) showed a round area of hyperintense FLAIR signal centered within the pons associated with central restricted diffusion, peripheral enhancement, and small paramagnetic low susceptibility signal foci consistent with petechial hemorrhage. Positron emission tomography (PET), perfusion MRI, and MR spectroscopy revealed no evidence of tumor recurrence. The diagnosis of SMART syndrome is presumed from the conventional and advanced imaging findings, clinical history, and clinical course.

Mechanisms and Origins of Spinal Pain: from Molecules to Anatomy, with Diagnostic Clues and Imaging Findings.

Spinal pain, especially low back pain (LBP), is a widespread clinical and diagnostic problem for both patients and physicians, because back pain has an equivalently wide variety of causes and provocations. Because of its variable nature and manifestations, back pain is challenging to diagnose and treat correctly. In addition, the pain is induced not only by direct mechanical pressure such as a herniated disk or degenerated bone but also by inflammation and associated proinflammatory cytokines. To help guide further diagnostic workup or the next step in management, radiologists should be familiar with the causes, mechanisms, and diagnostic clues provided by MRI. The authors review the microscopic and macroscopic mechanisms for each category of LBP and depict the relationship between imaging findings and pain mechanisms. This review focuses on the detailed anatomy related to the pain-signaling pathway and the roles of chemicals in inducing different mechanisms of LBP. MRI findings that serve as representative examples of key concepts are demonstrated according to each mechanism, and treatment options are reviewed on the basis of different causes of LBP. By knowing these concepts, radiologists can help correlate imaging findings with potential underlying mechanisms and help guide clinicians in the management of LBP. ©RSNA, 2020.

Amygdala enlargement in mesial temporal lobe epilepsy: an alternative imaging presentation of limbic epilepsy.

PURPOSE: To assess imaging, clinical, and pathological features of mesial temporal lobe epilepsy (mTLE) patients with amygdala enlargement (AE) in comparison with those with mesial temporal sclerosis (MTS). METHODS: Clinical, imaging, and pathologic features were retrospectively reviewed in 40 mTLE patients with postoperative follow-up (10 with AE and 30 with MTS). The volumes and signal intensity of the amygdala and hippocampus were assessed in 10 AE, 10 age- and sex-matched MTS patients, and 12 controls (HC). RESULTS: AE patients had a lower rate of concordant FDG PET (p < 0.05) and required more frequently intracerebral electrodes compared to MTS patients (p < 0.05). AE had larger ipsilateral amygdala (p < 0.0001) and hippocampus volumes (p < 0.0001) compared to MTS and to HC, with no significant differences for other brain structures. Normalized FLAIR signal was higher in the ipsilateral than contralateral amygdala in both AE and MTS (p < 0.001 and p < 0.05, respectively) and higher in the ipsilateral amygdala compared to HC (p < 0.05). In MTS, ADC in the ipsilateral amygdala (867 mm2/s) was higher compared to the contralateral one (804.8 × 10-6 mm2/s, p < 0.01), compared to HC (773 × 10-6 mm2/s, p < 0.01) and compared to the ipsilateral amygdala in AE (813.7 × 10-6 mm2/s, p < 0.05). AE patients had dysplasia (50%) or astrocytic gliosis (50%) of the amygdala extending to the hippocampus and temporal isocortex, and only 2/10 cases had pathologic findings of MTS. CONCLUSION: AE patients have distinct imaging and pathologic features compared to MTS, and require more extensive preoperative workup. Recognition of AE may improve preoperative assessment in TLE surgical candidates.

Roles of the apparent diffusion coefficient and tumor volume in predicting tumor grade in patients with choroid plexus tumors.

PURPOSE: To explore the utility of the apparent diffusion coefficient (ADC) and tumor volume to predict histological grade and prognosis in patients with choroid plexus tumors. METHODS: ADC and tumor volumes were retrospectively evaluated in 25 patients with choroid plexus papilloma (CPP; WHO grade 1 [n = 13]), atypical CPP (aCPP; grade 2 [n = 8]), or choroid plexus carcinoma (grade 3 [n = 4]) The prognostic roles of ADC and tumor volume were assessed. RESULTS: There were significant differences in mean and minimum ADC values, and tumor volume among the WHO grades (p = 0.033, p = 0.044, and p = 0.014, respectively). Receiver-operating characteristic analysis revealed a mean cutoff ADC value ≤ 1.397 × 10-3 mm2/s for aCPP (sensitivity = 0.667, specificity = 0.923). Multiple linear regression analysis demonstrated that both mean ADC (ß = - 0.455, p = 0.005) and tumor volume (ß = 0.513, p = 0.002) were correlated with WHO grade (adjusted R2 = 0.520, p = 0.005). Kaplan-Meier curve analysis identified poorer survival in patients with WHO grade 2 and 3 tumors than in those with WHO grade 1 disease (p = 0.049 and p = 0.012, respectively). A mean ADC ≤ 1.397 × 10-3 mm2/s (p = 0.001) and tumor volume 21.05 ml (p = 0.031) predicted significantly poorer survival. CONCLUSION: Mean ADC and tumor volume were correlated with WHO grade of choroid plexus tumors. A lower ADC value and a larger tumor volume predicted a poorer prognosis.

Genetic Syndromes Associated with Central Nervous System Tumors.

Several genetic tumor syndromes have associated central nervous system (CNS) neoplasms. The spectrum of syndromes that have intracranial tumor manifestations includes ataxia telangiectasia, Cowden syndrome, familial adenomatous polyposis, hereditary non-polyposis-related colorectal cancer, Li-Fraumeni syndrome, Gorlin syndrome, neurofibromatosis types 1 and 2, multiple endocrine neoplasia type 1, tuberous sclerosis complex, von Hippel-Lindau disease, and Turcot syndrome. Many of these disorders are inherited in an autosomal dominant fashion, and identification of the associated genetic defects has led to improved understanding of the molecular pathways involved in tumorigenesis, helping pave the way to the emergence of molecularly targeted therapeutics. Recognition of individuals and families at risk for such tumors is critical to improve clinical care and optimize proper genetic counseling. To contribute effectively, the radiologist should recognize the common varieties of tumors and characteristic neuroimaging manifestations seen in each familial syndrome. A fundamental understanding of the genetics and molecular pathogenesis of these tumors is critical in understanding the development of specific and unique tumors in each entity. In this article, we review the most common genetic tumor syndromes with associated intracranial neoplasms, with emphasis on recent genetic and molecular biology data, clinical manifestations, and management as well as the controversies and current recommendations for screening and surveillance. A detailed overview of all the major and pertinent CNS imaging features will be elucidated, including computed tomography, magnetic resonance imaging, and, in relevant cases, magnetic resonance spectroscopy. ©RSNA, 2016.

Uncommon and Miscellaneous Inflammatory Disorders of the Brain and Spine.

Inflammatory disorders of the brain and spine have a highly variable MRI appearance, often demonstrating significant overlap in imaging features. The resulting diagnostic dilemma is particularly challenging when considering the more uncommon neuroinflammatory entities. Diligent examination of the salient clinical presentation and signal alteration on imaging examination is necessary when considering neuroinflammation as a diagnostic possibility and may aid in raising suspicion for a particular neuroinflammatory entity. This article reviews a selection of uncommon and miscellaneous inflammatory disorders of the brain and spine to raise awareness of the clinical and imaging features that may assist in this challenging diagnostic task.

Imaging of the Sinonasal Cavities.

This article describes the various abnormalities that affect the sinonasal cavities and discusses inflammations, tumors, and tumor-like conditions. Specific imaging evaluations that focus on the sinonasal cavities are described in more detail.

Utility of dynamic susceptibility contrast MRI for differentiation between paragangliomas and meningiomas in the cerebellopontine angle and jugular foramen region.

PURPOSE: Differentiation of paragangliomas and meningiomas can be a challenge. This study aimed to assess the utility of dynamic susceptibility contrast perfusion MRI (DSC-MRI) to distinguish paragangliomas from meningiomas. METHODS: This retrospective study included 40 patients with paragangliomas and meningiomas in the cerebellopontine angle and jugular foramen region between March 2015 and February 2022 in a single institution. Pretreatment DSC-MRI and conventional MRI were performed in all cases. Normalized relative cerebral blood volume (nrCBV), relative cerebral blood flow (nrCBF), relative mean transit time (nrMTT), and time to peak (nTTP) as well as conventional MRI features were compared between the 2 tumor types and between meningioma subtypes as appropriate. Receiver operating characteristic curve and multivariate logistic regression analysis were performed. RESULTS: Twenty-eight meningiomas including 8 WHO grade II meningiomas (12 males, 16 females; median age 55 years) and 12 paragangliomas (5 males, 7 females; median age 35 years) were included in this study. Paragangliomas had a higher rate of cystic/necrotic changes (10/12 vs 10/28; P = 0.014), a higher rate of internal flow voids (9/12 vs 8/28; P = 0.013), higher nrCBV (median 9.78 vs 6.64; P = 0.04), and shorter nTTP (median 0.78 vs 1.06; P < 0.001) than meningiomas. There was no difference in conventional imaging features and DSC-MRI parameters between meningioma subtypes. nTTP was identified as the most significant parameter for the 2 tumor types in the multivariate logistic regression analysis (P = 0.009). CONCLUSIONS: In this small retrospective study, DSC-MRI perfusion differences were observed between paragangliomas and meningiomas, but not between grade I and II meningiomas.

Neurological and Neuroradiological Manifestations in Neonates Born to Mothers With Coronavirus Disease 2019.

BACKGROUND: To investigate the complications that occurred in neonates born to mothers with coronavirus disease 2019 (COVID-19), focusing on neurological and neuroradiological findings, and to compare differences associated with the presence of maternal symptoms. METHODS: Ninety neonates from 88 mothers diagnosed with coronavirus disease 2019 (COVID-19) during pregnancy were retrospectively reviewed. Neonates were divided into two groups: symptomatic (Sym-M-N, n = 34) and asymptomatic mothers (Asym-M-N, n = 56). The results of neurological physical examinations were compared between the groups. Data on electroencephalography, brain ultrasound, and magnetic resonance imaging abnormalities were collected for neonates with neurological abnormalities. RESULTS: Neurological abnormalities at birth were found in nine neonates (Sym-M-N, seven of 34, 20.6%). Decreased tone was the most common physical abnormality (n = 7). Preterm and very preterm birth (P < 0.01), very low birth weight (P < 0.01), or at least one neurological abnormality on physical examination (P = 0.049) was more frequent in Sym-M-N neonates. All infants with abnormalities on physical examination showed neuroradiological abnormalities. The most common neuroradiological abnormalities were intracranial hemorrhage (n = 5; germinal matrix, n = 2; parenchymal, n = 2; intraventricular, n = 1) and hypoxic brain injury (n = 3). CONCLUSIONS: Neonates born to mothers with symptomatic COVID-19 showed an increased incidence of neurological abnormalities. Most of the mothers (96.4%) were unvaccinated before the COVID-19 diagnosis. Our results highlight the importance of neurological and neuroradiological management in infants born to mothers with COVID-19 and the prevention of maternal COVID-19 infection.

Brain MRI Findings of Hemophagocytic Lymphohistiocytosis With a Heterozygous PRF1 Gene Mutation Masquerading As CLIPPERS: A Case Report.

Familial hemophagocytic lymphohistiocytosis is a rare and potentially life-threatening genetic condition characterized by unsuppressed immune activation and hypercytokinemia. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is a central nervous system inflammatory disorder characterized by punctate and curvilinear gadolinium-enhancing lesions in the brainstem, cerebellum, and spinal cord, which responds well to corticosteroid treatment. Hemophagocytic lymphohistiocytosis has been known to mimic CLIPPERS on neuroimaging, and patients previously diagnosed with CLIPPERS may carry familial hemophagocytic lymphohistiocytosis-related gene mutations that serve as predisposing factors. In this article, we describe a case initially diagnosed with CLIPPERS based on characteristic magnetic resonance imaging features and clinical course, who was later diagnosed with hemophagocytic lymphohistiocytosis based on a heterozygous familial hemophagocytic lymphohistiocytosis-associated PRF1 gene mutation.

Intracranial paragangliomas versus schwannomas: Role of dynamic susceptibility contrast perfusion and diffusion MRI.

BACKGROUND AND PURPOSE: Differentiating paragangliomas from schwannomas and distinguishing sporadic from neurofibromatosis type 2 (NF 2)-related schwannomas is challenging but clinically important. This study aimed to assess the utility of dynamic susceptibility contrast perfusion MRI (DSC-MRI) and diffusion-weighted imaging (DWI) in discriminating infratentorial extra-axial schwannomas from paragangliomas and NF2-related schwannomas. METHODS: This retrospective study included 41 patients diagnosed with paragangliomas, sporadic schwannomas, and NF2-related schwannomas in the infratentorial extra-axial space between April 2013 and August 2021. All cases had pretreatment DSC-MRI and DWI. Normalized mean apparent diffusion coefficient (nADCmean), normalized relative cerebral blood volume (nrCBV), and normalized relative cerebral blood flow (nrCBF) were compared between paragangliomas and schwannomas and between sporadic and NF2-related schwannomas as appropriate. RESULTS: nrCBV and nrCBF were significantly higher in paragangliomas than in sporadic/NF2-related schwannomas (nrCBV: median 11.5 vs. 1.14/3.74; p < .001 and .004, nrCBF: median 7.43 vs. 1.13/2.85; p < .001 and .007, respectively), while nADCmean were not. The corresponding diagnostic performances were area under the curves (AUCs) of .99/.92 and 1.0/.90 with cutoffs of 2.56/4.22 and 1.94/3.36, respectively. nADCmean were lower, and nrCBV and nrCBF were higher in NF2-related than in sporadic schwannomas (nADCmean: median 1.23 vs. 1.58, nrCBV: median 3.74 vs. 1.14, nrCBF: median 2.85 vs. 1.13; all p < .001), and the corresponding diagnostic performances were AUCs of .93, .91, and .95 with cutoffs of 1.37, 2.63, and 2.48, respectively. CONCLUSIONS: DSC-MRI and DWI both can aid in differentiating paragangliomas from schwannomas and sporadic from NF2-related schwannomas.

Neurofibromatosis type 2 versus sporadic vestibular schwannoma: The utility of MR diffusion and dynamic contrast-enhanced imaging.

BACKGROUND AND PURPOSE: The goal of this study was to assess the utility of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to distinguish sporadic vestibular schwannomas (VSs) from those related to neurofibromatosis type 2 (NF2). METHODS: We retrospectively reviewed 265 patients pathologically diagnosed with VSs between January 2015 and October 2020 in a single institution. There were 28 patients (male: 19, female: 9; age 11-67 years) including 23 sporadic and five NF2-related VSs, who had pretreatment DWI and DCE-MRI. Normalized mean apparent diffusion coefficient (nADCmean) and DCE-MRI parameters along with tumor characteristics were compared between sporadic and NF2-related VSs as appropriate. The diagnostic performances were calculated based on the receiver operating characteristic curve analysis for the values that showed significant differences. To identify significant modalities, multivariate logistic regression analysis was performed using nADCmean and the combination of statistically significant DCE-MRI parameters. RESULTS: NADCmean, fractional volume of extracellular space (Ve), and forward volume transfer constant (Ktrans) were significantly different between sporadic and NF2-related VSs (nADCmean: median 1.62 vs. 1.16, P = .002; Ve: median 0.40 vs. 0.66, P = .007; Ktrans: median 0.17 vs. 0.33, P = .007), whereas fractional plasma volume (Vp), reverse reflux rate constant (Kep), and tumor characteristics were not. The diagnostic performances of nADCmean, Ve, and Ktrans were 0.93, 0.90, and 0.90 area under the curves with cutoffs of 1.46, 0.51, and 0.29, respectively. nADCmean and the combination of Ve and Ktrans were both chosen as significant differentiators by multivariate logistic regression analysis (P = .027). CONCLUSIONS: DWI and DCE-MRI are both promising modalities to distinguish sporadic and NF2-related VSs.