Outcome of epidural blood patch for imaging-negative spontaneous intracranial hypotension.

BACKGROUND: Spontaneous intracranial hypotension is diagnosed by an abnormal finding in brain MRI, spinal imaging, or lumbar puncture. However, the sensitivity of each test is low. We investigated whether patients with suspected spontaneous intracranial hypotension and negative imaging findings would respond to epidural blood patch. METHODS: We prospectively recruited patients with new-onset orthostatic headache admitted at the Samsung Medical Center from January 2017 to July 2021. In patients without abnormal imaging findings and no history of prior epidural blood patch, treatment outcome-defined as both 50% response in maximal headache intensity and improvement of orthostatic component-was collected at discharge and three months after epidural blood patch. RESULTS: We included 21 treatment-naïve patients with orthostatic headache and negative brain and spinal imaging results who received epidural blood patch. After epidural blood patch (mean 1.3 times, range 1-3), 14 (66.7%) and 19 (90.5%) patients achieved both 50% response and improvement of orthostatic component at discharge and three months post-treatment, respectively. Additionally, complete remission was reported in 11 (52.4%) patients at three-month follow-up, while most of the remaining patients had only mild headaches. Among nine (42.9%) patients who underwent lumbar puncture, none had an abnormally low opening pressure (median 13.8 cm H2O, range 9.2-21.5). CONCLUSION: Given the high responder rates of epidural blood patch in our study, empirical epidural blood patch should be considered to treat new-onset orthostatic headache, even when brain and spinal imaging are negative. The necessity of lumbar puncture is questionable considering the high response rate of epidural blood patch and low rate of "low pressure."

Diagnostic performance of a high-spatial-resolution voxelwise analysis of neuromelanin-sensitive imaging in early-stage idiopathic Parkinson's disease.

BACKGROUND: Quantitative assessments of neuromelanin (NM) of the substantia nigra pars compacta (SNpc) in neuromelanin-sensitive MRI (NM-MRI) to determine its abnormality have been conducted by measuring either the volume or contrast ratio (CR) of the SNpc. A recent study determined the regions in the SNpc that are significantly different between early-stage idiopathic Parkinson's disease (IPD) patients and healthy controls (HCs) using a high spatial-resolution NM-MRI template, which enables a template-based voxelwise analysis to overcome the susceptibility of CR measurement to inter-rater discrepancy. We aimed to assess the diagnostic performance, which has not been reported, of the CRs between early-stage IPD patients and HCs using a NM-MRI template. METHODS: We retrospectively enrolled early-stage IPD patients (n = 50) and HCs (n = 50) who underwent 0.8-mm isovoxel NM-MRI and dopamine-transporter PET as the standard of reference. A template-based voxelwise analysis revealed two regions in nigrosomes 1 and 2 (N1 and N2, respectively), with significant differences in each substantia nigra (SNpc) between IPD and HCs. The mean CR values of N1, N2, volume-weighted mean of N1 and N2 (N1 + N2), and whole SNpc on each side were compared between IPD and HC using the independent t-test or the Mann-Whitney U test. The diagnostic performance was compared in each region using receiver operating characteristic curves. RESULTS: The mean CR values in the right N1 (0.149459 vs. 0.194505), left N1 (0.133328 vs. 0.169160), right N2 (0.230245 vs. 0.278181), left N2 (0.235784 vs. 0.314169), right N1 + N2 (0.155322 vs. 0.278143), left N1 + N2 (0.140991 vs. 0.276755), right whole SNpc (0.131397 vs. 0.141422), and left whole SNpc (0.127099 vs. 0.137873) significantly differed between IPD patients and HCs (all p < 0.001). The areas under the curve of the left N1 + N2, right N1 + N2, left N1, right N1, left N2, right N2, left whole SNpc, and right whole SNpc were 0.994 (sensitivity, 98.0%; specificity, 94.0%), 0.985, 0.804, 0.802, 0.777, 0.766, 0.632, and 0.606, respectively. CONCLUSION: Our NM-MRI template-based CR measurements revealed significant differences between early-stage IPD patients and HCs. The CR values of the left N1 + N2 demonstrated the highest diagnostic performance.

Three-dimensional double-echo steady-state with water excitation magnetic resonance imaging to localize the intraparotid facial nerve in patients with deep-seated parotid tumors.

PURPOSE: To assess the utility of three-dimensional double-echo steady-state with water excitation (3D-DESS-WE) imaging for localizing deep-seated parotid tumors in relation to the facial nerve. METHODS: A prospective study comparing the surgical outcomes of parotidectomy with or without 3D-DESS-WE sequence is currently enrolling the patients. Magnetic resonance imaging data from the first 25 patients with 3D-DESS-WE sequence were reviewed. Visibility of the intraparotid facial nerve was independently assessed by two neuroradiologists. The diagnostic performance of the 3D-DESS-WE sequence for prediction of deep lobe involvement was compared with that of two conventional methods based on the retromandibular vein line (RMVL) and facial nerve line (FNL). The relationship between the tumor and the main trunk of the facial nerve was also evaluated on the 3D-DESS-WE sequence. RESULTS: On 3D-DESS-WE images, the main trunk, temporofacial division, and cervicofacial division of the intraparotid facial nerve were visualized in 100% (25/25), 48% (12/25), and 36% (9/25) of patients, respectively. The diagnostic accuracy of the 3D-DESS-WE sequence for prediction of deep lobe involvement was 92% (23/25), which was significantly superior to that of the RMVL (68% [17/25]; p = 0.008) and FNL (64% [16/25]; p = 0.004) methods. The relationship between the tumor and the main trunk of the facial nerve was correctly predicted in 92% (23/25) of 3D-DESS-WE images. CONCLUSION: By direct visualization of the facial nerve, the 3D-DESS-WE sequence improved the preoperative localization of the intraparotid facial nerve in deep-seated parotid tumors. This information may help better surgical planning for deep-seated parotid tumors.

Radiologic findings and the molecular expression profile of diffuse midline glioma H3 K27M mutant.

BACKGROUND: Diffuse midline glioma H3 K27M-mutant (DMG) are reported to show heterogeneous radiologic imaging features in children. We hypothesized that other genetic mutations may contribute to this heterogeneity. PURPOSE: To describe the magnetic resonance imaging (MRI) findings of DMG in adult patients and to correlate the imaging findings with the molecular expression profile. MATERIAL AND METHODS: Eighteen patients with pathologically proven DMG were enrolled. On preoperative MRI, the following were evaluated: location; size of the lesion; ratio of non-enhancing (NE) and contrast-enhancing (CE) area; presence of cortical invasion and necrotic component; maximum relative cerebral blood volume ratio (rCBV ratio) of NE and CE portions; and minimum apparent diffusion coefficient (ADC) of NE and CE portions, among others. Molecular profiles including ATRX expression and p53 mutation were reviewed to find correlation with imaging features. RESULTS: Thalamus was the most commonly involved location, followed by pons and tectum. Five patients showed loss of normal ATRX expression. p53 mutation was positive in 12 patients. 40% of normal ATRX expression patients had cortical involvement and 20% had leptomeningeal seeding; none of the patients with ATRX loss had cortical involvement or leptomeningeal seeding. Patients with normal ATRX expression showed significantly higher rCBV ratio and lower ADC value in the NE area than patients with ATRX loss (P=0.04, 0.016). p53 mutation status did not correlate with any imaging finding. CONCLUSION: Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.

Diagnostic accuracy of MR imaging of patients with leptomeningeal seeding from lung adenocarcinoma based on 2017 RANO proposal: added value of contrast-enhanced 2D axial T2 FLAIR.

PURPOSE: We purposed to compare diagnostic accuracy of contrast-enhanced (CE) 3D T1-weighted fast field echo (3D T1-WI), CE 2D spin echo T1-weighted image (2D T1-WI), and CE 2D T2 FLAIR on evaluation of leptomeningeal metastasis(LM) using detailed features suggested in RANO proposal in a homogeneous group with cytology-proven LM. METHODS: Thirty-five lung adenocarcinoma patients with CSF cytology-proven leptomeningeal metastasis were enrolled in this retrospective analysis, who were enrolled in the prospective study (NCT03257124). MR images including CE 3D T1-WI, CE 2D T1-WI, and CE 2D FLAIR were reviewed. Presence of leptomeningeal nodule, leptomeningeal enhancement, and cranial nerve enhancement was evaluated according to the RANO proposal. Diagnostic accuracy of each sequence was compared and added value of CE 2D FLAIR to CE 3D T1-WI was evaluated. RESULTS: Two patients had unmeasurable small nodules recognized on 3D T1-WI only. Leptomeningeal enhancement was positive in 60%, 60%, and 77.1%, cranial nerve enhancement was positive in 51.4%, 45.7%, and 68.6% of the patients on 3D T1-WI, 2D T1-WI, and 2D FLAIR, respectively. Overall sensitivity for detection of LM was 71.4%, 71.4%, and 82.9% on 3D T1-WI, 2D T1-WI, and 2D FLAIR. When adding 2D FLAIR to 3D T1-WI, overall sensitivity for detection of LM was 82.9%. CONCLUSION: 3D T1-WI is the best for identifying leptomeningeal nodules. The sensitivity of 2D FLAIR is the highest for both LNE and CNE. Since both sequences are complementary, it can be helpful to take both sequences. Checking each feature according to the RANO proposal, especially CNE, may help you not to miss LM.

LIMK1/2 are required for actin filament and cell junction assembly in porcine embryos developing in vitro.

OBJECTIVE: This study was conducted to investigate the roles of LIM kinases (LIMK1 and LIMK2) during porcine early embryo development. We checked the mRNA expression patterns and localization of LIMK1/2 to evaluate their characterization. We further explored the function of LIMK1/2 in developmental competence and their relationship between actin assembly and cell junction integrity, specifically during the first cleavage and compaction. METHODS: Pig ovaries were transferred from a local slaughterhouse within 1 h and cumulus oocyte complexes (COCs) were collected. COCs were matured in in vitro maturation medium in a CO2 incubator. Metaphase II oocytes were activated using an Electro Cell Manipulator 2001 and microinjected to insert LIMK1/2 dsRNA into the cytoplasm. To confirm the roles of LIMK1/2 during compaction and subsequent blastocyst formation, we employed a LIMK inhibitor (LIMKi3). RESULTS: LIMK1/2 was localized in cytoplasm in embryos and co-localized with actin in cell-to-cell boundaries after the morula stage. LIMK1/2 knockdown using LIMK1/2 dsRNA significantly decreased the cleavage rate, compared to the control group. Protein levels of E-cadherin and ß-catenin, present in adherens junctions, were reduced at the cell-to-cell boundaries in the LIMK1/2 knockdown embryos. Embryos treated with LIMKi3 at the morula stage failed to undergo compaction and could not develop into blastocysts. Actin intensity at the cortical region was considerably reduced in LIMKi3-treated embryos. LIMKi3-induced decrease in cortical actin levels was attributed to the disruption of adherens junction and tight junction assembly. Phosphorylation of cofilin was also reduced in LIMKi3-treated embryos. CONCLUSION: The above results suggest that LIMK1/2 is crucial for cleavage and compaction through regulation of actin organization and cell junction assembly.

Corrigendum to: Cytoplasmic polyadenylation element binding protein 2 (CPEB2) is required for tight-junction assembly for establishment of porcine trophectoderm epithelium.

Cytoplasmic polyadenylation element binding protein (CPEB) is an RNA-binding protein that promotes elongation of poly(A) tails and regulates mRNA translation. CPEB depletion in mammary epithelium is known to disrupt tight-junction (TJ) assembly via mislocalisation of tight junction protein 1 (TJP1), but the role of CPEB in the biological functions associated with TJs has not yet been studied. The objective of this study was to investigate the roles of CPEB2 during porcine parthenote development. CPEB2 was detected in both the nuclei and apical cytoplasm at the 4- and 8-cell stages and was localised to cell-cell contact after the initiation of the morula stage. Its depletion led to retarded blastocyst formation caused by impaired TJ assembly. Moreover, transcription of TJ-associated genes, including TJP1, Coxsackie virus and adenovirus receptor (CXADR) and occludin (OCLN), was not affected, but the corresponding proteins were not properly localised at the apical cell membrane in morulae, suggesting that CPEB2 confers mRNA stability or determines subcellular localisation for translation. Remarkably reduced relative levels of TJP1 transcripts bearing the 3'-untranslated region were noted, indicating that CPEB2 mediates TJP1 mRNA stability. In conclusion, our findings demonstrate that because of its regulation of TJP1, CPEB2 is required for TJ assembly during porcine blastocyst development.

Cytoplasmic polyadenylation element binding protein 2 (CPEB2) is required for tight-junction assembly for establishment of porcine trophectoderm epithelium.

Cytoplasmic polyadenylation element binding protein (CPEB) is an RNA-binding protein that promotes elongation of poly(A) tails and regulates mRNA translation. CPEB depletion in mammary epithelium is known to disrupt tight-junction (TJ) assembly via mislocalisation of tight junction protein 1 (TJP1), but the role of CPEB in the biological functions associated with TJs has not yet been studied. The objective of this study was to investigate the roles of CPEB2 during porcine parthenote development. CPEB2 was detected in both the nuclei and apical cytoplasm at the 4- and 8-cell stages and was localised to cell-cell contact after the initiation of the morula stage. Its depletion led to retarded blastocyst formation caused by impaired TJ assembly. Moreover, transcription of TJ-associated genes, including TJP1, Coxsackie virus and adenovirus receptor (CXADR) and occludin (OCLN), was not affected, but the corresponding proteins were not properly localised at the apical cell membrane in morulae, suggesting that CPEB2 confers mRNA stability or determines subcellular localisation for translation. Remarkably reduced relative levels of TJP1 transcripts bearing the 3'-untranslated region were noted, indicating that CPEB2 mediates TJP1 mRNA stability. In conclusion, our findings demonstrate that because of its regulation of TJP1, CPEB2 is required for TJ assembly during porcine blastocyst development.

Increasing discrepancy of MR imaging and CSF study in patients with leptomeningeal seeding from lung adenocarcinoma after targeted therapy using a tyrosine kinase inhibitor.

PURPOSE: To evaluate the correlation between contrast-enhanced (CE) MRI and cerebrospinal fluid (CSF) cytology for the evaluation of leptomeningeal metastasis (LM) on MRI after targeted therapy with tyrosine kinase inhibitors. METHODS: We retrospectively reviewed the data of nonsmall cell lung cancer patients registered with NCT03257124 from May 2017 to December 2018, with progressive disease despite targeted therapy. Twenty-nine patients whose MRI scans exhibited LM at the time of registration were enrolled. During the targeted therapy with osimertinib, MRI scans, and subsequent CSF examinations were performed in every 2 months. In total, 113 MRI scans and CSF cytology data after treatment were collected. For each CE MRI scan, LM positivity was evaluated on 3D T1-weighted image (T1WI) and 2D FLAIR. The correlation between MRI and CSF cytology results and the diagnostic performance of MRI with CSF cytology as a reference standard were evaluated. RESULTS: After treatment, MRI revealed positivity for LM in 81 and negativity in 32. CSF results were positive in 69 examinations and negative in 44. The diagnostic accuracy of CE 3D T1WI and 2D FLAIR was 0.52 and 0.46, respectively. After targeted therapy, discrepancy in the CSF and MRI results tended to increase over time. The proportions of concordant MRI and CSF cytology results after targeted therapy were 66%, 58%, 62%, and 47% at the first, second, third, and fourth follow-up, respectively. CONCLUSION: The discrepancy of MRI in evaluation of LM and CSF cytology increases over time after targeted therapy with osimertinib. LM positivity on MRI could be a surrogate imaging marker in the pre- and immediate posttargeted-treatment with Osimertinib but not after sessions of osimertinib.

Neuroretinitis after the second injection of a SARS-CoV-2-vaccine: A case report.

Purpose: We report the first case of neuroretinitis after administration of a second dose of a messenger RNA vaccine for coronavirus disease-2019 (COVID-19). Observations: An 83-year-old healthy woman presented with subacute, painless, and progressive visual loss in the right eye that started 2 days after the second injection of the COVID-19 vaccine (Comirnaty®) from Pfizer (New York, NY, USA) and BioNTech (Mainz, Germany). Visual acuities were hand motion perception in the right eye and 20/30 in the left eye. There was optic nerve head swelling in the right eye and subretinal fluid and disruption of the photoreceptor layers in both eyes. Magnetic resonance imaging revealed an enhancement of the right optic nerve, consistent with optic neuritis. She was treated with intravenous corticosteroids, and the optic nerve swelling in the right eye resolved promptly. However, the amount of subretinal fluid worsened for 1 month and did not improve until 6 months from onset. Her visual acuity was slightly improved to finger count perception in the right eye and 20/20 in the left eye during an examination 6 months from onset. Conclusions and Importance: Considering the temporal relation between the second dose of vaccination and the symptom onset in our patient, the ophthalmic symptoms here reported might be considered a rare adverse effect of the Comirnaty® COVID-19 vaccine. Although a causal relationship is not established, to our knowledge, this is the first report of neuroretinitis after vaccination with Comirnaty®, and any further similar cases should be examined in detail.

Vessel Wall Changes on Serial High-Resolution MRI and the Use of Cilostazol in Patients With Adult-Onset Moyamoya Disease.

BACKGROUND AND PURPOSE: The natural course of adult-onset moyamoya disease (MMD) is unknown, and there is no medical treatment that halts its progression. We hypothesized that progressive shrinkage of large intracranial arteries occurs in adult-onset MMD, and that cilostazol inhibits this process. METHODS: Serial high-resolution magnetic resonance imaging (HR-MRI) was performed on 66 patients with MMD: 30 patients received cilostazol, 21 received other antiplatelets, and 15 received no antiplatelets or had poor compliance to them. Serial HR-MRI was performed (interval between MRI scans: 29.67±18.02 months, mean±SD), and changes in outer diameter, luminal stenosis, and vascular enhancement were measured. Factors affecting HR-MRI changes were evaluated, including vascular risk factors and the ring finger protein 213 gene variant. RESULTS: The progression of stenosis to occlusion, recurrent ischemic stroke, and the development of new stenotic segments were observed in seven, seven, and three patients, respectively. Serial HR-MRI indicated that the degree of stenosis increased with negative remodeling (outer diameter shrinkage). Patients who received cilostazol presented significantly larger outer diameters and lower degrees of stenosis compared with other groups (p=0.005 and p=0.031, respectively). After adjusting for clinical and genetic factors, only cilostazol use was independently associated with negative remodeling (odds ratio=0.29, 95% confidence interval=0.10-0.84, p=0.023). While vascular enhancement was observed in most patients (61 patients), the progression of enhancement or the occurrence of new vascular enhancement was rarely observed on follow-up HR-MRI (6 and 1 patients, respectively). CONCLUSIONS: Adult-onset MMD induces progressive shrinkage of large intracranial arteries, which cilostazol treatment may prevent. Further randomized clinical trials are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02074111.

Body CT and PET/CT detection of extracranial lymphoma in patients with newly diagnosed central nervous system lymphoma.

BACKGROUND: We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease. METHODS: An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared. RESULTS: One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001). CONCLUSION: Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.

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Because of the inherent complex anatomy and functional arrangement of the cranial nerves (CNs), neuroimaging of cranial neuropathy is challenging. With recent advances in magnetic resonance imaging (MRI) techniques, the cause of cranial neuropathy can now be detected in many cases. As an active multidisciplinary team member of cranial neuropathy, it is essential for the neuroradiologist to be familiar with the detailed anatomy of the CNs on MRI. This review contains the basic MRI anatomy of CNs III-XII according to a segmental classification from the brain stem to the extracranial region. The optimal imaging options to best evaluate the specific segment of the CNs will also be discussed briefly.

Ultrasound Strain Elastography for Circumscribed Solid Thyroid Nodules without Malignant Features Categorized as Indeterminate by B-Mode Ultrasound.

The aim of this study was to evaluate the diagnostic performance of ultrasound strain elastography (USE) for circumscribed solid thyroid nodules without malignant or benign features seen on US. This retrospective study included 197 thyroid nodules in 196 patients who underwent USE with color mapping and strain ratio measurement between 2010 and 2014. Of the 197 nodules, 24 (12.2%) were malignant. No significant differences in color mapping or strain ratio were observed between benign and malignant nodules. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 29.2% (95% confidence interval [CI]: 13.8%-49.4%), 77.5% (95% CI: 75.3%-80.3%), 15.2% (95% CI: 7.2%-25.8%), 88.7% (95% CI: 86.3%-92.0%), and 71.6% (95% CI: 67.8%-76.5%) for color mapping and 50.0% (95% CI: 30.%-69.5%), 57.2% (95% CI: 54.5%-59.9%), 14.0% (95% CI: 8.5%-18.4%), 89.2% (95% CI: 85.0%-93.4%) and 56.3% (95% CI: 51.6%-61.1%) for strain ratio measurement, respectively. USE with color mapping and strain ratio measurement has a limited ability to differentiate benign from malignant nodules for circumscribed solid thyroid nodules without definite malignant features categorized as indeterminate by B-mode US.

Radiologic Findings of Primary Mucinous Cystadenocarcinoma of the Breast: A Report of Two Cases and a Literature Review.

Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare but pathologically distinct breast tumor. There have been some case reports on primary MCA of the breast; however, they have all focused on pathologic findings. Here, we report the radiologic findings of two cases of MCA along with a review of the literature. Breast MCA shows a circumscribed mass with some calcifications on mammography, an intracystic solid mass without increased vascularity or a vascular stalk on ultrasound, and a heterogeneously enhancing mass within a rim-enhancing cyst with intermediate signal intensity on T2-weighted magnetic resonance imaging. These radiologic findings and the presence of mucin in the percutaneous biopsy specimen should suggest the possibility of MCA in the differential diagnosis of a breast tumor.

Pancreatic Candidiasis That Mimics a Malignant Pancreatic Cystic Tumor on Magnetic Resonance Imaging: A Case Report in an Immunocompetent Patient.

Candida is a commensal organism that is frequently found in the human gastrointestinal tract. It is the most common organism that causes pancreatic fungal infections. However, magnetic resonance imaging findings of Candida infection in the pancreas have not been described. We report imaging findings of pancreatic candidiasis in a patient in immunocompetent condition. It presented as a multi-septated cystic mass with a peripheral solid component in the background of pancreatitis and restricted diffusion on diffusion-weighted image that mimicked a malignant pancreatic cystic tumor.