MRI Pattern Research Articles

Rare helminthic variants in ophthalmologic practice in the Far East

In this work, we carry out a literature review into the current knowledge of the rarest ophthalmic helminthoses, including approaches to their timely diagnosis and effective therapy. In terms of their rarity, ocular forms of helminthoses should be classified into relatively frequent forms, such as toxocarosis, and rarer forms, such as those with the infestation of the visual organ and the development of paragonimiasis and dirofilariosis. The epidemiology of ocular onchocerciasis in the Far East of the Russian Federation is not only exclusively imported, but also has an orphan prevalence. The lack of adequate biomicroscopic visualization of the causative agent of dirofilariasis is the main limiting factor in the management of these patients, which affects both diagnosis and treatment. The masquerade syndrome in the clinical course of paragonimiasis is a factor that prioritizes anamnestic findings, which are most often confined to the consumption of an additional host, most often improperly processed crayfish. Ophthalmologic and cerebral forms require radiologic imaging with detection of characteristic MRI patterns. At the current stage of medicine development, drug therapy is sufficient to resolve the pathologic process in ocular paragonimiasis. Ophthalmologists should carry out a more comprehensive assessment of the somatic status of each patient resistant to primary, often empirical, therapy in order to exclude parasitological causes.

Bacterial Meningoencephalitis in Newborns

Bacterial meningoencephalitis in newborns is a severe and life-threatening pathology, which results from meningeal infection and the subsequent involvement of the brain parenchyma. The severity of the acute onset of symptoms and the risk of neurodevelopmental adverse sequelae in children strongly depend on the timing of the infection, the immunological protection transmitted by the mother to the fetus during pregnancy, and the neonate’s inflammatory and immune system response after birth. Although the incidence of neonatal meningitis and meningoencephalitis and related mortality declined in the past twenty years with the improvement of prenatal care and with the introduction of intrapartum antibiotic prophylaxis against Streptococcus beta Hemolyticus group B (Streptococcus Agalactiae) in the 1990s, bacterial meningitis remains the most common form of cerebrospinal fluid infection in pediatric patients. To date, the rate of unfavorable neurological outcomes is still from 20% to 60%, and the possibility of containing its rate strongly depends on early diagnosis, therapy, and a multidisciplinary approach, which involves neonatologists, neurologists, neuroradiologists, and physiotherapists. Neonatal meningitis remains difficult to diagnose because the responsible bacteria vary with gestational age at birth, age at presentation, and environmental context. The clinical presentation, especially in the newborn, is very ambiguous. From a clinical point of view, the definitive test for diagnosis is lumbar puncture in patients with symptoms suggestive of neurological involvement. Therefore, neuroimaging is key for raising clinical suspicion of meningitis or corroborating the diagnosis based on clinical and laboratory data. Our pictorial review offers a practical approach to neonatal meningoencephalitis by describing the epidemiology, the pathophysiology of bacterial meningoencephalitis, defining the indications and suggesting optimized protocols for neuroimaging techniques, and showing the main neuroimaging findings to reach the diagnosis and offering proper follow-up of bacterial meningitis. Moreover, we tried identifying some peculiar MRI patterns related to some bacteria.

Pictorial Review of Rare Pancreatic Tumors and Tumor-like Lesions: Radiologic–Pathologic Correlation

Rare pancreatic tumors and non-neoplastic tumor-like lesions present a diagnostic challenge due to their uncommon occurrence and overlapping imaging characteristics with more prevalent pancreatic neoplasms. Advances in imaging technologies and diagnostic criteria have contributed to increased detection of these rare entities in clinical practice. This pictorial review focuses on the radiologic–pathologic correlation of rare pancreatic tumors, including colloid carcinoma, acinar cell carcinoma, pancreatoblastoma, primary pancreatic lymphoma, and non-neoplastic tumor-like lesions such as hamartomas and inflammatory pseudotumors. Detailed imaging features, such as signal intensities on MRI and enhancement patterns on CT, are correlated with pathological findings to assist in the differential diagnosis. Familiarity with these characteristics is crucial for radiologists to ensure accurate diagnosis and guide appropriate treatment strategies, as management and prognosis significantly differ from common pancreatic neoplasms.

Features of Magnetic Resonance Diagnostics of Tenosynovial Giant Cell Tumor (Pigmented Villonodular Synovitis)

Aim. Demonstrate the features of magnetic resonance diagnostics of tenosynovial giant cell tumor.Materials and Methods. Using magnetic resonance imaging, we identified patients with tenosynovial giant cell tumor of the knee joint, describing the diagnostic features and clinical course of diffuse and local forms of the tumor.Results. Specific MRI patterns of tenosynovial giant cell tumor are hemosiderin deposits, villous and nodular growths of the synovium of the knee joint, joint effusion and bone erosion.Conclusion. Тenosynovial giant cell tumor is a rare mesenchymal neoplasm arising from the synovium of joints and tendon sheaths, disabling young able-bodied people. Magnetic resonance imaging, being the “gold” standard for radiological diagnostics, helps to identify specific patterns.

Imaging Findings and MRI Patterns in a Cohort of 18q Chromosomal Abnormalities.

The abnormalities of the long arm of chromosome 18 (18q) constitute a complex spectrum. We aimed to systematically analyze their MR imaging features. We hypothesized that there would be variable but recognizable white matter and structural patterns in this cohort. In this retrospective cohort study, we included pediatric patients with a proved abnormality of 18q between 2000-2022. An age- and sex-matched control cohort was also constructed. Thirty-six cases, median MR imaging age 19.6 months (4.3-59.3), satisfied our inclusion criteria. Most were female (25, 69%, F:M ratio 2.2:1). Fifty MR imaging studies were analyzed, and 35 (70%) had delayed myelination. Two independent readers scored brain myelination with excellent interrater reliability. Three recognizable evolving MR imaging patterns with distinct age distributions and improving myelination scores were identified: Pelizaeus-Merzbacher disease-like (9.9 months, 37), intermediate (22 months, 48), and washed-out pattern (113.6 months, 53). Etiologically, MRIs were analyzed across 3 subgroups: 18q deletion (34, 69%), trisomy 18 (10, 21%), and ring chromosome 18 (5, 10%). Ring chromosome 18 had the highest myelination lag (27, P = .005) and multifocal white matter changes (P = .001). Trisomy 18 had smaller pons and cerebellar dimensions (anteposterior diameter pons, P = .002; corpus callosum vermis, P < .001; and transverse cerebellar diameter, P = .04). In this cohort of 18q chromosomal abnormalities, MR imaging revealed recognizable patterns correlating with improving brain myelination. Imaging findings appear to be on a continuum with more severe white matter abnormalities in ring chromosome 18 and greater prevalence of structural abnormalities of the pons and cerebellum in trisomy 18.

234 - Comparative study of image quality between T2-weighted FRFSE and PROPELLER based on respiratory patterns of abdominal MRI

234 - Comparative study of image quality between T2-weighted FRFSE and PROPELLER based on respiratory patterns of abdominal MRI

Differential inclusion of NEB exons 143 and 144 provides insight into NEB-related myopathy variant interpretation and disease manifestation

Biallelic pathogenic variants in the gene encoding nebulin (NEB) are a known cause of congenital myopathy. We present two brothers with congenital myopathy and compound heterozygous variants (NC_000002.12:g.151692086G>T; NM_001271208.2: c.2079C>A; p.(Cys693Ter) and NC_000002.12:g.151533439T>C; NM_001271208.2:c.21522+3A>G ) in NEB. Transcriptomic sequencing on affected individual muscle revealed that the extended splice variant c.21522+3A>G causes exon 144 skipping. Nebulin isoforms containing exon 144 are known to be mutually exclusive with isoforms containing exon 143, and these isoforms are differentially expressed during development and in adult skeletal muscles. Affected individuals MRI patterns of muscle involvement were compared to the known pattern of relative abundance of these two isoforms in muscle. We propose that the pattern of muscle involvement in these affected individuals better fits the distribution of exon 144-containing isoforms in muscle than with previously published MRI findings in NEB-related disease due to other variants. Our report introduces disease pathogenesis and manifestation as a result of alteration of isoform distributions in muscle.

Redefining the phenotype of alpha-methylacyl-CoA racemase (AMACR) deficiency

BackgroundAlpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal enzyme deficiency caused by biallelic variants in the AMACR gene. This deficiency leads to the accumulation of toxic bile acid intermediates (R)-trihydroxycholestenoic acid (THCA) and (R)-dihydroxycholestenoic acid (DHCA) and pristanic acid. With less than 20 patients described in literature, the phenotype of AMACR deficiency is poorly defined and no data on the natural history are available.ResultsHere we describe a cohort of 12 patients (9 adults and 3 children) with genetically confirmed AMACR deficiency (median age at diagnosis 56 years, range 3–69), followed for an average of 6 years (between 2015 and 2023). Five novel pathogenic variants are described. In 5/9 adult patients, retinitis pigmentosa was detected at a median age of 45 years (range 30–61). The median delay to diagnosis of AMACR deficiency after the diagnosis of retinitis pigmentosa was 24 years (range 0–33). All adult patients subsequently developed neurological signs and symptoms after the age of 40 years; most frequently neuropathy, ataxia and cognitive decline with prior normal cognitive functioning. One patient presented with a stroke-like episode. All adult patients showed a typical MRI pattern involving the thalami and gray matter structures of the pons and midbrain. One patient had a hepatocellular carcinoma at the time of the AMACR deficiency diagnosis and two patients suffered from gallstones. All three included children had elevated liver transaminases as single presenting sign and showed no brain MRI abnormalities.ConclusionAMACR deficiency can be considered as an adult slowly progressive disease with a predominant neurological phenotype. The main signs comprise retinitis pigmentosa, neuropathy, ataxia and cognitive decline; stroke-like episodes may occur. Recognition of typical MRI abnormalities may facilitate prompt diagnosis. In addition, there is a risk of liver fibrosis/cirrhosis and hepatocellular carcinoma in these patients, requiring active monitoring.

Perfusion-weighted MRI patterns in neuropsychiatric systemic lupus erythematosus: a systematic review and meta-analysis.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a complex manifestation of Systemic Lupus Erythematosus (SLE) characterized by a wide range of neurological and psychiatric symptoms. This study aims to elucidate the patterns of Perfusion-Weighted MRI (PWI) in NPSLE patients compared to SLE patients without neuropsychiatric manifestations (non-NPSLE) and healthy controls (HCs). A systematic search was conducted in PubMed/Medline, Embase, Web of Science, and Scopus for studies utilizing PWI in NPSLE patients published through April 14, 2024. Cerebral blood flow (CBF) data from NPSLE, non-NPSLE patients, and HCs were extracted for meta-analysis, using standardized mean difference (SMD) as an estimate measure. For studies lacking sufficient data for inclusion, CBF, cerebral blood volume (CBV), and mean transit time (MTT) were reviewed qualitatively. Our review included eight observational studies employing PWI techniques, including dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL). The meta-analysis of NPSLE compared to non-NPSLE incorporated four studies, encompassing 104 NPSLE patients and 90 non-NPSLE patients. The results revealed an SMD of -1.42 (95% CI: -2.85-0.00, I2: 94%) for CBF in NPSLE compared to non-NPSLE. PWI reveals informative patterns of cerebral perfusion, showing a significant reduction in mean CBF in NPSLE patients compared to non-NPSLE patients. Our qualitative synthesis highlights these changes, particularly in the frontal and temporal lobes. However, the existing data exhibits considerable heterogeneity and limitations.

Typical and atypical MRI patterns of rare brain disorders: Thechallenge of low numbers.

Typical and atypical MRI patterns of rare brain disorders: Thechallenge of low numbers.

Association of Gestational Age at Birth and Changes on MRI With Prevalence and Spectrum of Comorbidities in Children With Cerebral Palsy.

For individuals with cerebral palsy (CP) and caregivers, comorbidities may be a greater challenge than neuromotor impairment. Clinicians may make assumptions regarding risk of comorbidities based simply on term vs preterm birth, but this has not been well examined. To better understand factors affecting comorbidity pattern, we investigated the relationship between gestational age (GA) and imaging pattern on the presence of specific comorbidities. This is a cross-sectional study of data extracted from the Canadian Cerebral Palsy Registry of children with CP. Multivariable analysis was used to evaluate the relationship between brain injury, GA, and comorbidities. Comorbidities included in the analysis were communication, cognitive, visual, and auditory impairment, seizures in the past year, and gavage feeding. Each comorbidity was assessed as a separate nonexclusive outcome, with GA, MRI pattern, birth weight, postneonatal insult, 5-minute Apgar score, and male sex considered as potential modifiers. The only comorbidity affected by GA on multivariable analysis was seizures within the past year that were more prevalent in term children (odds ratio [OR] 1.1 95% CI 1.0-1.2) and was also affected by Apgar score (OR 0.9 95% CI 0.85-0.94), but not MRI pattern. MRI pattern appeared important for communication impairment (deep gray OR 4.2 95% CI 1.8-10.0; total brain injury OR 8.5, 95% CI 3.2-22.6; malformation OR 2.7, 95% CI 1.3-5.7) and cognitive impairment (deep gray OR 5.6, 95% CI 2.4-13.2; total brain injury OR 10.1, 95% CI 4.0-25.3; malformation OR 3.3, 95% CI 1.6-6.8; watershed OR 3.6, 95% CI 1.4-8.9). Focal injury compared with normal MRI was associated with reduced odds of visual impairment (OR 0.24, 95% CI 0.12-0.48), auditory impairment (OR 0.2195% CI 0.10-0.46) and communication impairment (OR 0.46, 95% CI 0.26-0.82), and overall number of comorbidities (coefficient -0.73, 95% CI -1.2 to -0.31). The number of comorbidities was increased by total brain injury pattern (coefficient 0.65, 95% CI 0.15-1.13) and reduced by focal brain injury (coefficient -0.73, 95% CI -1.2 to -0.31) and increasing 5-minute Apgar score (coefficient -0.11, 95% CI -0.16 to -0.07). In those with brain injuries sufficient to cause CP, development of additional comorbidities is less affected by GA at birth and more related to the underlying cause of CP as reflected by MRI patterns.

Patterns of brain volume and metabolism predict clinical features in the progressive supranuclear palsy spectrum.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that presents with highly heterogenous clinical syndromes. We perform cross-sectional data-driven discovery of independent patterns of brain atrophy and hypometabolism across the entire PSP spectrum. We then use these patterns to predict specific clinical features and to assess their relationship to phenotypic heterogeneity. We included 111 patients with PSP (60 with Richardson syndrome and 51 with cortical and subcortical variant subtypes). Ninety-one were used as the training set and 20 as a test set. The presence and severity of granular clinical variables such as postural instability, parkinsonism, apraxia and supranuclear gaze palsy were noted. Domains of akinesia, ocular motor impairment, postural instability and cognitive dysfunction as defined by the Movement Disorders Society criteria for PSP were also recorded. Non-negative matrix factorization was used on cross-sectional MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans. Independent models for each as well as a combined model for MRI and FDG-PET were developed and used to predict the granular clinical variables. Both MRI and FDG-PET were better at predicting presence of a symptom than severity, suggesting identification of disease state may be more robust than disease stage. FDG-PET predicted predominantly cortical abnormalities better than MRI such as ideomotor apraxia, apraxia of speech and frontal dysexecutive syndrome. MRI demonstrated prediction of cortical and more so sub-cortical abnormalities, such as parkinsonism. Distinct neuroanatomical foci were predictive in MRI- and FDG-PET-based models. For example, vertical gaze palsy was predicted by midbrain atrophy on MRI, but frontal eye field hypometabolism on FDG-PET. Findings also differed by scale or instrument used. For example, prediction of ocular motor abnormalities using the PSP Saccadic Impairment Scale was stronger than with the Movement Disorders Society Diagnostic criteria for PSP oculomotor impairment designation. Combination of MRI and FDG-PET demonstrated enhanced detection of parkinsonism and frontal syndrome presence and apraxia, cognitive impairment and bradykinesia severity. Both MRI and FDG-PET patterns were able to predict some measures in the test set; however, prediction of global cognition measured by Montreal Cognitive Assessment was the strongest. MRI predictions generalized more robustly to the test set. PSP leads to neurodegeneration in motor, cognitive and ocular motor networks at cortical and subcortical foci, leading to diverse yet overlapping clinical syndromes. To advance understanding of phenotypic heterogeneity in PSP, it is essential to consider data-driven approaches to clinical neuroimaging analyses.

Imaging Biomarkers for Differential Diagnosis of Central Nervous System Inflammatory Diseases

Inflammatory diseases of the central nervous system (CNS) include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis. In addition, various rheumatoid autoimmune diseases, autoimmune encephalitis, and medications such as immune checkpoint inhibitors can cause inflammation in the CNS. Radiological findings are very useful for us in differentiating inflammatory diseases of the CNS. On MRI, the shape, location, length/size, and gadolinium enhancement pattern of the lesions as well as the recovery and atrophy of the lesions following the acute phase, serve as important biomarkers for differentiating the diseases. In this review, we will highlight the typical characteristics MRI of optic neuritis, brain lesions, and myelitis in MS, NMOSD, and MOGAD, and outline the features of other inflammatory diseases of CNS.

Imaging Biomarkers for Differential Diagnosis of Central Nervous System Inflammatory Diseases

Inflammatory diseases of the central nervous system (CNS) include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and acute disseminated encephalomyelitis. In addition, various rheumatoid autoimmune diseases, autoimmune encephalitis, and medications such as immune checkpoint inhibitors can cause inflammation in the CNS. Radiological findings are very useful for us in differentiating inflammatory diseases of the CNS. On MRI, the shape, location, length/size, and gadolinium enhancement pattern of the lesions as well as the recovery and atrophy of the lesions following the acute phase, serve as important biomarkers for differentiating the diseases. In this review, we will highlight the typical characteristics MRI of optic neuritis, brain lesions, and myelitis in MS, NMOSD, and MOGAD, and outline the features of other inflammatory diseases of CNS.

Low circulating tumor cell levels correlate with favorable outcomes and distinct biological features in multiple myeloma.

There is growing interest in multiple myeloma (MM) circulating tumor cells (CTCs), but their rareness in peripheral blood (PB) and inconsistency in cutoffs question their clinical utility. Herein, we applied next-generation flow cytometry in 550 bone marrow (BM) and matched PB samples to define an optimal CTC cutoff for both transplant-eligible and transplant-ineligible newly diagnosed MM (NDMM) patients. Deep phenotyping was performed to investigate unique microenvironmental features associated with CTC dissemination. CTCs were detected in 90% of patients (median 0.01%; range: 0.0002%-12.6%) and increased levels associated with adverse features. Correlations were observed between high CTC percentages and a diffused MRI pattern, a distinct BM composition characterized by altered B-cell differentiation together with an expansion of effector cells and tumor-associated macrophages, as well as a greater phenotypic dissimilarity between BM and PB clonal cells. Progression-free survival (PFS) and overall survival (OS) gradually worsened with each logarithmic increment of CTCs. Conversely, NDMM patients without CTCs showed unprecedented outcomes, with 5-year PFS and OS rates of 83% and 97%, respectively. A cutoff of 0.02% CTCs was independent of the ISS, LDH, and cytogenetics in a multivariate analysis of risk factors for PFS. The 0.02% CTC cutoff synergized with the MGUS-like phenotype and the R-ISS for improving the risk stratification systems. MRD negativity was less frequent if CTCs were ≥0.02% at diagnosis, but whenever achieved, the poor prognosis of these patients was abrogated. This study shows the clinical utility of CTC assessment in MM and provides evidence toward a consensus cutoff for risk stratification.

HIGH ANKLE SPRAINS WITH SYNDESMOSIS INSTABILITY: TIME TO MRI MATTERS

IntroductionEarly clinical examination combined with MRI following a high ankle sprain allows accurate diagnosis of syndesmosis instability. However, patients often present late, and for chronic injuries clinical assessment is less reliable. Furthermore, in many centres MRI may be not be readily available. The aims of the current study were to define MRI characteristics associated with syndesmosis instability, and to determine whether MRI patterns differed according to time from injury.MethodsRetrospectively, patients with an unstable ligamentous syndesmosis injury requiring fixation were identified from the logbooks of two fellowship trained foot and ankle surgeons over a five-year period. After exclusion criteria (fibula fracture or absence of an MRI report by a consultant radiologist), 164 patients (mean age 30.7) were available. Associations between MRI characteristics and time to MRI were examined using Pearson's chi-square tests or Fisher's exact tests (significance set at p&lt; 0.05).ResultsOverall, 100% of scans detected a syndesmosis injury if performed acutely (within 6 weeks of injury), falling to 83% if performed after 12 weeks (p=0.001). In the acute group, 93.5% of patients had evidence of at least one of either PITFL injury (78.7%), posterior malleolus bone oedema (60.2%), or a posterior malleolus fracture (15.7%). In 20% of patients with a posterior malleolus bone bruise or fracture, the PITFL was reported as normal. The incidence of posterior malleolus bone bruising and fracture did not significantly differ according to time.ConclusionFor unstable ligamentous syndesmosis injuries, MRI becomes less sensitive over time. Importantly, posterior malleolus bone oedema or fracture may be the only evidence of a posterior injury. Failure to recognise instability may lead to inappropriate management of the patient, long term pain and arthritis. We therefore advocate early MRI as it becomes more difficult to ‘grade’ the injury if delayed.

The Contribution of Vessel Wall Magnetic Resonance Imaging to the Diagnosis of Primary and Secondary Central Nervous System Vasculitis.

To describe high-resolution brain vessel wall MRI (VW-MRI) patterns and morphological brain findings in central nervous system (CNS) vasculitis patients. Fourteen patients with confirmed CNS Vasculitis from two tertiary centers underwent VW-MRI using a 3T scanner. The images were reviewed by two neuroradiologists to assess vessel wall enhancement characteristics and locations. Fourteen patients were included (six females; average age 48 ± 19 years). Diagnoses included primary CNS vasculitis (PCNSV) in six patients and secondary CNS vasculitis (SCNSV) in eight, half of which were infection-related. Thirteen patients showed vessel wall enhancement, which was intense in eleven patients (84.6%) and concentric in twelve (92.3%), affecting the anterior circulation in nine patients (69.2%), posterior in two patients (15.4%), and both circulations in two patients (15.4%). The enhancement patterns were similar across different CNS vasculitis types. DWI changes corresponded with areas of vessel wall enhancement in 77% of patients. Conclusions: CNS vasculitis is often associated with intense, concentric vessel wall enhancement in VW-MRI, especially in the anterior circulation. The consistent presence of DWI alterations in affected territories suggests a possible link to microembolization or hypoperfusion. These imaging findings complement parenchymal brain MRI and MRA/DSA data, potentially increasing the possibility of a clinical diagnosis of CNS vasculitis.

Negative magnetic resonance imaging cannot be used to omit an initial prostate biopsy - An ambispective study

IntroductionUp to 40% of patients with suspected prostate cancer (PCa) have a negative prebiopsy magnetic resonance imaging (nMRI), and up to 15% of them may have clinically significant PCa (csPCa). The ability to predict the presence of csPCa despite nMRI may help avoid unnecessary biopsies. We aimed to determine the negative predictive value (NPV) of mpMRI, the influence of MRI reporting patterns in clinical practice, and the factors that might predict csPCa among men with an nMRI. MethodologyIn an IRB-approved, ambispective study, men who underwent prostate biopsy from 2016 to 2023 and had a prebiopsy MRI, were included to determine the presence of csPCa. The reporting patterns of institutional and noninstitutional MRI were evaluated. Age, digital rectal examination (DRE) findings, prostate specific antigen (PSA), PSA density (PSAD), and MRI reports were evaluated for their ability to predict csPCa in men with nMRI. Results1660 patients who underwent prostate biopsy were assessed for eligibility, and 685 patients were enrolled in the study. The median age, PSA and PSAD were 60 years, 11.63 ng/ml and 0.23 ng/ml/cm3, respectively. 62 (9%) men had an nMRI, among which csPCa, non-csPCa, and negative biopsy were found in 34%, 5%, and 61% of men, respectively. 61% had an institutional MRI, while 39% had a noninstitutional MRI. The sensitivity and NPV of any MRI for csPCa were 93% and 66%, respectively, which improved to 96% and 81% for institutional MRI. Univariate and multivariate analyses showed abnormal DRE and PSAD ≥0.25 ng/ml/cc as predictive factors for csPCa in men with an nMRI. Conclusion34% of men with negative MRIs were found to harbor csPCa on prostate biopsy. The NPV of institutional MRI was higher than for noninstitutional MRI. Men with an abnormal DRE or PSAD ≥0.25 ng/ml/cc had a higher incidence of csPCa despite an nMRI.

Clinical, Neuroimaging, and Metabolic Footprint of the Neurodevelopmental Disorder Caused by Monoallelic HK1 Variants.

Hexokinase 1 (encoded by HK1) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic HK1 variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals. We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic HK1 variants and an NDD phenotype. All individuals had recurrent variants likely causing gain-of-function, representing mutational hot spots. Eight individuals (c.1370C>T) had a developmental and epileptic encephalopathy with infantile onset and virtually no development. Of the other 7 individuals (n = 6: c.1334C>T; n = 1: c.1240G>A), 3 adults showed a biphasic course of disease with a mild static encephalopathy since early childhood and an unanticipated progressive deterioration with, e.g., movement disorder, psychiatric disease, and stroke-like episodes, epilepsy, starting in adulthood. Individuals who clinically presented in the first months of life had (near)-normal initial neuroimaging and severe cerebral atrophy during follow-up. In older children and adults, we noted progressive involvement of basal ganglia including Leigh-like MRI patterns and cerebellar atrophy, with remarkable intraindividual variability. The CSF glucose and the CSF/blood glucose ratio were below the 5th percentile of normal in almost all CSF samples, while blood glucose was unremarkable. This biomarker profile resembles glucose transporter type 1 deficiency syndrome; however, in HK1-related NDD, CSF lactate was significantly increased in all patients resulting in a substantially different biomarker profile. Genotype-phenotype correlations appear to exist for HK1 variants and can aid in counseling. A CSF biomarker profile with low glucose, low CSF/blood glucose, and high CSF lactate may point toward monoallelic HK1 variants causing an NDD. This can help in variant interpretation and may aid in understanding the pathomechanism. We hypothesize that progressive intoxication and/or ongoing energy deficiency lead to the clinical phenotypes and progressive neuroimaging findings.

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.