Gadolinium Contrast Enhancement Research Articles

Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis

Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy. To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD). This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023. MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features. Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala. In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.

Bilateral optic neuritis and encephalopathy as the atypical presentations of multiple sclerosis following severe acute respiratory syndrome coronavirus 2 infection

Abstract: Numerous evidence suggests coronavirus disease 2019 (COVID-19) potentially triggers demyelinating diseases, inclusive of multiple sclerosis (MS), and acute disseminated encephalomyelitis (ADEM), and various mechanisms have been proposed. We report a 42-year-old male presented with bilateral optic neuritis and encephalopathy, 2 weeks following COVID-19 infection. He denied any history or family history of neurological and ocular diseases. Severe bilateral visual impairment (only light perception) and pain with eye movement were reported. Fundoscopy revealed bilateral optic disc swelling. Magnetic resonance imaging showed tortuous bilateral optic nerves with optic nerve and nerve sheath enhancement. Multiple hyperintense nodules in bilateral cerebral white matter were noted on fluid-attenuated inversion recovery T2-weighted imaging without diffusion restriction or gadolinium contrast enhancement. Hypointense nodules in cerebral white matter were also noted on T1-weighted imaging, which implied some old lesions. Dissemination in space and time and cerebrospinal fluid-specific oligoclonal bands confirmed the diagnosis of MS. Both serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies were negative. He received pulse steroid therapy for 5 days, followed by slowly tapering oral prednisolone. His vision, ocular motion pain, and encephalopathy improved gradually. However, the visual outcome was still poor (bilateral 20/400), and optic atrophy was noticed during 1-year follow-up. To our knowledge, this is the first case of MS following severe acute respiratory syndrome coronavirus 2 infection presented with bilateral optic neuritis and encephalopathy. Since these manifestations are exceedingly rare in MS, we suspect acute immune reactions induced by COVID-19 could bring about the atypical ADEM-like presentations of MS.

A case of neurosarcoidosis initially diagnosed as cervical spondylotic myelopathy, leading to diagnosis by gadolinium contrast-enhanced MRI

A 70-year-old female presented with bilateral numbness in her upper limbs. She was diagnosed with cervical spondylotic myelopathy and underwent cervical laminoplasty. However, there was no significant improvement in sensory disturbance, and at 6 months after surgery, she developed subacute motor and gait disturbance in four extremities. Spinal MRI revealed a long lesion of the spinal cord with edema, and a part of the lesion showed gadolinium contrast enhancement. Bronchoscopy revealed an elevated CD4/8 ratio, and gallium scintigraphy demonstrated an accumulation in the hilar lymph nodes, leading to a diagnosis of neurosarcoidosis. In case of rapid deterioration during the course of cervical spondylotic myelopathy, neurosarcoidosis should be considered as a differential diagnosis, which can be assessed by contrast-enhanced MRI.

MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

Accuracy of International Classification of Diseases Codes for Identifying Acute Optic Neuritis.

The accuracy of International Classification of Diseases (ICD) codes for identifying cases of acute optic neuritis (aON) is not known. A prior study reported 61% accuracy for ICD code plus MRI consistent with aON within 2 months. This study determined accuracy for ICD code plus MRI within 2 months regardless of results. Retrospective chart review was conducted using a medical record research repository of a tertiary care institution from 1998 to 2019. Subjects with ICD-9/10 codes for ON and an MRI brain and/or orbits within 2 months of earliest (initial) ICD code were included. MRI was classified as positive or negative for aON based on report noting gadolinium-contrast enhancement. Clinical diagnosis at the time of initial code was classified as aON, prior ON, considered ON, alternative diagnosis, or unknown based on review of physician authored clinical notes within 7 days of the initial code. Accuracy of ICD code for aON, acute or prior ON, and acute, prior, or considered ON were calculated for all subjects and stratified based on MRI result. Two hundred fifty-one subjects had MRI results within 2 months of their initial ON ICD code (49 positive MRI [previously reported]; 202 negative MRI). Among those with negative MRI, 32 (16%) had aON, 40 (20%) had prior ON, 19 (9%) considered ON as a diagnosis, 92 (46%) had other confirmed diagnoses, and 19 (9%) had unknown diagnosis at time of code. Considering all subjects, accuracy for ICD code was 25% for acute ON, 41% for acute or prior ON, and 48% for acute, prior, or considered ON. Positive MRI, increased number of ON ICD codes, a code given by an ophthalmologist or neurologist within 2 months, and the presence of a neurology encounter within 2 months were associated with an increased accuracy for clinical aON diagnosis. In the setting of an MRI within 2 months, ICD codes for ON have low accuracy for acute ON and only slightly better accuracy for acute or prior ON. Accuracy is higher for cases with a positive MRI than those with a negative MRI, suggesting positive MRI in conjunction with ICD codes may help more accurately identify cases. Reliance on ICD and Current Procedural Terminology codes alone to identify aON cases may introduce substantial misclassification bias in claims-based research.

Comparison of 1.5 Tesla and 3.0 Tesla Magnetic Resonance Imaging in the Evaluation of Acute Demyelinating Optic Neuritis.

Optic neuritis (ON) is the most common optic neuropathy in young adults. MRI is reported to have a high sensitivity for ON. Higher signal strengths of MRI may enhance resolution and lead to better detection of ON. We sought to compare the sensitivity of 3.0 Tesla (T) MRI to that of 1.5 T MRI in detecting acute demyelinating ON. A retrospective chart review was performed on patients with a clinical diagnosis of optic neuritis at Mayo Clinic Health System from January 2010 to April 2020. Among 1,850 patients identified, 126 patients met the eligibility criteria. Exclusion criteria comprised questionable or alternative diagnosis, diagnosis of ON before the study period, eye examinations performed elsewhere, or absence of fat-saturated head and orbits MRIs performed locally within 30 days of symptom onset. Gadolinium contrast enhancement, T2 hyperintensity, and the radiologic diagnosis of ON were recorded by a neuro-radiologist who was masked to the clinical history and the magnet strength of the MRI. Fifty-three patients (42.1%) had 3.0 T MRI, and 73 patients (57.9%) had 1.5 T MRI. Overall, 88.9% (112/126) of patients were determined to have a positive MRI for ON. The radiographic sensitivity for ON was higher in the 3.0 T group compared with the 1.5 T group (98.1% vs 82.2%, respectively [ P = 0.004]). The frequency of gadolinium enhancement was found to be greater in the 3 T group compared with the 1.5 T group (98.1% vs 76.7%, respectively [ P &lt; 0.001]). T2 hyperintensity was also more often seen in the 3.0 T group compared with the 1.5 T group (88.7% vs 68.5%, respectively [ P = 0.01]). 3.0 T MRI is more sensitive than 1.5 T MRI in detecting ON. This finding suggests that 3.0 T MRI is a preferred imaging modality for the confirmation of ON.

Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial

RationaleThe long-acting β2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY.ObjectivesThe primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured.MethodsThis double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days.Measurements and main resultsOf 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial.ConclusionsIND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT02634983).

Relationship between molecular characteristics of glioblastoma multiforme and the subventricular zone

Objective This study aims to assess the relationship between the molecular characteristics of glioblastoma multiforme (GBM) and the subventricular zone (SVZ) Material and Methods Eligible patients had their data anonymously collected from an institutional database, including age, sex, preoperative performance status, the extent of tumour resection, anatomical location, IDH mutation and MGMT methylation status. An Institutional picture archiving and communications system was used for volumetric and morphometric analysis. All measurements were made on T1-weighted magnetic resonance images with gadolinium contrast enhancement. IDH wild-type and mutant GBMs were stratified by MGMT methylation status. The relationship between tumour volume, distance from the tumour’s enhancing edge and the tumour’s geometric centre to the SVZ and their molecular characteristics were assessed. Results Fifty IDH wild-type GBMs were studied. Twenty-three were MGMT methylated, Twenty-seven were unmethylated. IDH wild-type MGMT methylated GBMs were significantly associated with a tumour’s enhancing boundary being contiguous to the SVZ (P < 0.001). Ninety percent of tumours contiguous to the SVZ were wild-type methylated (n = 18) and 10% were unmethylated (n = 2). Mean GBM geometric centre distance to SVZ was significantly less for methylated wild-type GBMs compared to unmethylated (P = 0.025) and median GBM distance from the tumour’s edge of enhancement to the SVZ was significantly shorter in methylated tumours compared to unmethylated (P < 0.001). Mean and median distances to SVZ from the edge of enhancement was 3.8 millimetres (mm) and 0 mm, respectively, for wild-type methylated GBMs, while for unmethylated wild-types, 14.6 mm, and 12.5 mm. There was no anatomical localisation of IDH wild-type GBMs by MGMT methylation status to a cerebral hemisphere or lobe. Conclusion IDH wild-type GBMs contiguous to the SVZ are highly likely to be MGMT methylated. Replication by further studies is required to affirm our results and conclusion.

The diagnostic value of contrast enhancement on MRI in diffuse and anaplastic gliomas.

We evaluated differentiations in gadolinium contrast enhancement (CE) between low-grade WHO °II and high-grade WHO °III gliomas in conventional MRI, which have been repeatedly questioned. Ninety-nine patients, who underwent first resection of WHO°II and °III gliomas, were retrospectively retrieved from a prospective database. The quantitative metric volume of Gd-CE in T1-weighted pre-operative MRI was measured using volumetric segmentation. The OR to detect CE in anaplastic gliomas was seven times higher than that in diffuse gliomas (CI95% 2.8-17.2,p<0.0001). No CE was seen in 50% (8/16) of focal anaplastic and in 28% (10/36) of entirely anaplastic gliomas. CE was present in 21% (10/47) of diffuse gliomas. Anaplasia correlated with a larger CE volume (r=0.49, p<0.0001) and provided additional 4 cm3of CE volume compared to entirely diffuse tumors. The OR to have CE was 3.6 times for IDH1 wild-type tumors (CI95% 1.3-10.2, p=0.05) and 4.8 for tumors with ATRX expression (CI95% 1.3-17.2,p=0.05). In all sub-groups, at least a quarter of cases showed no CE at all and there were cases with present CE. CE is associated with higher odds of unfavorable prognostic features like anaplasia, wild-type IDH1 and retained ATRX. There was no CE in one-fourth of anaplastic gliomas and half of gliomas with focal anaplasia.

Fluorescence real-time kinetics of protoporphyrin IX after 5-ALA administration in low-grade glioma.

5-Aminolevulinic acid (5-ALA) induces fluorescence in high-grade glioma (HGG), which is used for resection. However, the value of 5-ALA-induced fluorescence in low-grade glioma (LGG) is unclear. Time dependency and time kinetics have not yet been investigated. The purpose of this study was to investigate real-time kinetics of protoporphyrin IX (PpIX) in LGG based on hyperspectral fluorescence-based measurements and identify factors that predict fluorescence. Patients with grade II gliomas and imaging from which HGGs could not be completely ruled out received 5-ALA at 20 mg/kg body weight 4 hours prior to surgery. Fluorescence intensity (FI) and PpIX concentration (CPpIX) were measured in tumor tissue utilizing a hyperspectral camera. Apparent diffusion coefficient (ADC)-based tumor cell density, Ki-67/MIB-1 index, chromosomal 1p/19q codeletion, and 18F-fluoroethyl-l-tyrosine (18F-FET) PET values and their role for predicting fluorescence were evaluated. Eighty-one biopsies from 25 patients were included. Tissues with fluorescence demonstrated FI and CPpIX maxima between 7 and 8 hours after administration. When visible fluorescence was observed, peaks of FI and CPpIX were observed within this 7- to 8-hour time frame, regardless of any MRI gadolinium contrast enhancement. Gadolinium enhancement (p = 0.008), Ki-67/MIB-1 index (p < 0.001), 18F-FET PET uptake ratio (p = 0.004), and ADC-based tumor cellularity (p = 0.017) significantly differed between fluorescing and nonfluorescing tissue, but not 1p/19q codeletions. Logistic regression demonstrated that 18F-FET PET uptake and Ki-67/MIB-1 index were independently related to fluorescence. This study reports a fluorescence-based assessment of CPpIX in human LGG tissues related to 18F-FET PET uptake and Ki-67/MIB-1. As in HGGs, fluorescence in LGGs peaked between 7 and 8 hours after 5-ALA application, which has consequences for the timing of administration.

Association Between Histopathology and Magnetic Resonance Imaging Texture in Grading Gliomas Based on Intraoperative Magnetic Resonance Navigated Stereotactic Biopsy.

To explore the value of magnetic resonance imaging (MRI) textures and its correlation with histopathological malignancy of gliomas by magnetic resonance (MR) navigated stereotactic biopsy. A total of 36 diffuse glioma cases and 64 puncture targets were included. All patients underwent a preoperative MR scan and intraoperative MR-navigated stereotactic biopsy. The histopathological diagnosis was grade II or grade III diffuse glioma. Regions of interest consistent with puncture targets were delineated on T1-weighted brain volume with gadolinium contrast enhancement images, and textures were extracted using Omni Kinetics software. Mann-Whitney rank sum test was used to analyze texture differences between grade II and grade III samples. False discovery rate (FDR) correction was applied to correct for multiple comparisons. Receiver operating characteristic curves evaluated the diagnostic value of textural analysis for grading gliomas. Correlation between MRI textures and histopathology was examined by Spearman correlation test. Texture features, including max intensity, 95th quantile, range, variance, standard deviation, sum variance, and cluster prominence were higher in grade III glioma targets than grade IIs, grade II gliomas showed increased uniformity and short run low gray-level emphasis values (P and qFDRcorr < 0.05). Area under the curve was 0.887 (95% confidence interval, 0.805-0.969; P < 0.001) with combined textures in glioma grading. The listed first-order and gray-level cooccurrence matrix textures were correlated with Ki-67 labeling index. Gray-level cooccurrence matrix and gray-level run length matrix textures were correlated with isocitrate dehydrogenase 1 mutation. Textures on T1-weighted brain volume with gadolinium contrast enhancement images differ between grade III and II gliomas and are correlated with Ki-67 labeling index and isocitrate dehydrogenase 1 mutation.

Clinical Findings of Thalamic and Brainstem Glioma Including Diffuse Midline Glioma, H3K27M Mutant:A Clinical Study

Diffuse midline glioma, H3K27M mutant is a glioma located in the thalamus, brainstem, or spine with the H3K27M mutation, which is a new entity in the 2016 revised WHO classification. The treatment of thalamic glioma(TG)and brainstem glioma(BSG), which includes diffuse midline gliomas, the H3K27M mutant is challenging, and there are no standard therapeutic strategies. It is important to determine the characteristics of these brain tumors. Here, we retrospectively reviewed 31 consecutive patients with TG and BSG who were treated at our institute between January 1994 and May 2018, including methionine-positron emission tomography(MET-PET)data. Fourteen patients had TG, while 17 patients had BSG. Six patients were children, and 25 were adults. Nine patients with TGs and seven with BSG were enhanced by gadolinium. Twenty-seven patients were treated with radiotherapy, and 20 patients were treated with chemotherapy. All 21 tumors that underwent surgery showed wild-type IDH. The H3K27M mutation was present in four TG and two BSG. There was no statistically significant association between methionine uptake and gadolinium contrast enhancement and tumor grade. The median overall survival period(OS)of all cases was 16.9 months, whereas those of TG and BSG were 22.8 and 10.0 months, respectively. Because TG and BSG still have poor prognoses, it is necessary to elucidate the pathology of the disease and establish its standard therapy.

Factors Associated With Increased Emergency Department Utilization in Patients With Acute Optic Neuritis.

Symptoms of acute vision loss and eye pain may lead patients with optic neuritis to seek care in the emergency department (ED). Given the availability of lower cost alternatives for providing medical care for optic neuritis, this study aimed to identify factors associated with higher ED utilization. Subjects with acute optic neuritis were identified through a chart review of adults with International Classification of Diseases-9 (ICD-9) or ICD-10 codes for optic neuritis with corresponding gadolinium contrast enhancement of the optic nerve on MRI in the medical record research repository of a tertiary care institution. Subjects were grouped based on the number of ED visits (0-1 and 2-3) within 2 months of either ICD code or MRI. Demographics, characteristics of disease presentation, type and location of medical care, testing (chest imaging, lumbar puncture, optical coherence tomography, spine MRI, visual field, and laboratory tests), treatment, provider specialty of follow-up visits, and duration of care were extracted from the medical record. Of 30 acute optic neuritis subjects (age 41 ± 16 years, range 18-76, 53% [16/30] female), 19 had 0-1 ED visit and 11 had 2-3 ED visits. Most subjects were Caucasian, non-Hispanic (47%), followed by Asian (23%), Hispanic/Latino (17%), Black (10%), and others (3%). Subjects had an initial clinical encounter primarily in the outpatient setting (63%) as compared with the ED (37%). The median time from symptom onset to initial clinical encounter was 4 days with a range of 0-13. Subjects were mostly insured through a private insurance (60%), followed by Medicare/Medicaid (23%) and uninsured (17%). Fewer ED visits were associated with an initial clinical encounter in an outpatient setting (P = 0.02, chi-square), but not residential distance from the hospital or insurance type. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). There was no significant difference in the ophthalmic, radiologic, or laboratory testing performed in both groups. Both groups presented in a similar time frame with similar symptoms and clinical signs. Treatment was similar in both groups. Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting and thus strategies aimed at facilitating outpatient care may help reduce unnecessary ED visits, although some, such as insurance status, may be difficult to modify. Further study in a larger sample is needed to refine these observations.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis: a report of two cases

BackgroundIgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.Case presentationTwo ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave’s disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.ConclusionsA high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

A case of primary intramedullary spinal cord lymphoma diagnosed by spinal cord biopsy of long spinal cord lesions showing persistent gadolinium contrast enhancement

An 82-year-old man presented with subacute bilateral lower limb paralysis, deep sensory disturbance, and vesico-rectal disturbance. MRI of the spinal cord revealed a large gray matter-dominant lesion extending from the medulla oblongata to the lower thoracic spinal cord. The patient was treated with steroid-pulse therapy for myelitis, but without symptomatic improvement. A spinal cord biopsy was performed for treatment-resistant myelopathy, and histopathology revealed a diffuse large B-cell lymphoma, that was diagnosed as a primary intramedullary spinal cord lymphoma because systemic examination didn't show any other findings suggestive of malignant lymphoma. A spinal cord biopsy is necessary for the definitive diagnosis of this disease, but in the case of poor response to treatment and a progressive course, intramedullary malignant lymphoma should be considered if there is a persistent elevation of CSF IL-10 or a prolonged contrast effect.

Two Cases with Acute Tumefactive non enhancing Demyelinating lesions; The Significance of Gadolinium Contrast enhancement in MRI (2385)

Two Cases with Acute Tumefactive non enhancing Demyelinating lesions; The Significance of Gadolinium Contrast enhancement in MRI (2385)

MRI Gadolinium Volume in Cerebral Adrenoleukodystrophy: A Novel Biomarker to Quantify Cerebral Inflammation and Predict Transplant Response.

Adrenoleukodystrophy (ALD) is caused by mutations within the X-linked <i>ABCD1</i> gene resulting in the inability to transport acylated very long chain fatty acids (VLCFA) into the peroxisome for degradation. VLCFA subsequently accumulate in tissues, including the central nervous system. Up to 40% of boys develop a severe, progressive demyelinating form of ALD, cerebral ALD (cALD), resulting in regions of demyelination observed on brain magnetic resonance imaging (MRI) that are associated with a "garland ring" of gadolinium contrast enhancement. Gadolinium enhancement indicates blood-brain-barrier (BBB) disruption and an active inflammatory disease process. Only hematopoietic cell transplant (HCT) is accepted as therapy sufficient to halt neurologic progression and resolve the observed gadolinium enhancement, although the mechanism of disease arrest is unknown. We have previously shown that rapid donor neutrophil recovery after HCT facilitates MRI gadolinium resolution. We now show early (28 days post HCT) gadolinium resolution correlates well with improved neurologic outcomes measured 1-year post HCT. We recently developed a method to quantify gadolinium on imaging and calculate a gadolinium (Gad) volume given in cubic centimeters (cc). We evaluated Gad volume and other previously described imaging and transplant related biomarkers in 66 boys who underwent HCT. In univariate analysis we found day 28 gadolinium resolution was associated with the following pre-transplant parameters: less Gad volume (7.3 cc versus 2.7 cc, p=0.01), less Gad intensity (p=0.04) and less extensive demyelination as determined by the Loes MRI scoring system (p=0.03). In addition, resolution of Gad enhancement by day 28 was associated with lower pre-HCT plasma and cerebral spinal fluid chitotriosidase activity (p=0.04 for both), and faster neutrophil recovery post HCT (less than 16 days versus greater than 16 days, p=0.03). Multivariate analysis revealed that only less Gad volume was predictive of rapid gadolinium resolution at 28 days post HCT (p = 0.02). This is the first data to quantify the extent of cerebral inflammation in cALD as defined by Gad positivity and its resolution after HCT. Future studies should consider use of Gad volume prior to HCT as a useful biomarker for time to resolution.

P476 Efficacy and safety of 2 vedolizumab IV regimens in patients with perianal fistulising Crohn’s disease: results of the ENTERPRISE study

Abstract Background Perianal fistulae occurring with Crohn’s disease (CD) are a challenge to treat. Vedolizumab (VDZ) is a gut-selective, monoclonal α 4β7 integrin antibody approved to treat patients (patients) with moderately to severely active CD. Here we report results from ENTERPRISE (NCT02630966; EudraCT 2015-000852-12), a randomised, double-blind, phase 4 trial to evaluate 2 VDZ IV dosing regimens in patients with fistulising CD. Methods Patients with moderately to severely active CD and 1–3 draining perianal fistulae received either VDZ 300 mg IV at Weeks (Week) 0, 2, 6, 14, and 22 (VDZ), or the same regimen plus an additional VDZ dose at Wk10 (VDZ+Wk10). The primary endpoint was the proportion of patients with a ≥50% reduction from baseline (BL) in the number of draining fistulae (absence of draining despite gentle finger compression) at Wk30. Secondary endpoints were the proportion of patients with a ≥50% reduction from BL in the number of draining fistulae at Wk22 and Wk30, and the proportion of patients with 100% fistulae closure at Wk30. Patients with missing data at study visits were counted as non-responders. Perianal disease activity index (PDAI), perianal pain score, Van Assche score, gadolinium contrast enhancement by pelvic MRI, and safety were assessed. Study enrolment closed early due to slow recruitment; thus, all analyses are descriptive. Results Of the 32 patients with post-BL assessment of fistulae healing (full analysis set, FAS), 28 had ≥1 draining fistula at BL (modified FAS). Median CD duration was 8.5 years (VDZ [n = 14]: 11.2 years; VDZ+ Week 10 [n = 14]: 6.1 years). In each arm, 11 patients (78.6%) had prior anti-tumour necrosis factor therapy at BL; concomitant corticosteroid use was 21.4% (VDZ) and 14.3% (VDZ+ Week 10), and concomitant immunosuppressant use was 28.6% (VDZ) and 21.4% (VDZ+ Week 10). At Wk30, 53.6% of all patients achieved ≥50% decrease in the number of draining fistulae (VDZ: 64.3%; VDZ+ Week 10: 42.9%; Figure 1). The proportion of patients with fistulae response increased rapidly and remained high through Week 30 (Figure 2); 46.4% of patients (VDZ: 57.1%; VDZ+Week 10: 35.7%) achieved ≥50% decrease in the number of draining fistulae at both Weeks 22 and 30. Closure of all fistulae draining at BL was observed at Week 30 in 42.9% of patients (VDZ: 50.0%; VDZ+ Week 10: 35.7%). In the FAS, mean (SD) PDAI scores changed from BL to Weeks 30–4.1 (3.3) and perianal pain scores changed –2.2 (2.7) (table). At Wk30, mean (SD) Van Assche scores and contrast enhancement scores changed –1.1 (3.1) and –9.5 (69.4) from screening, respectively. No new safety signals were observed. Conclusion Over half of CD patients treated with VDZ had reductions of ≥50% in the number of draining perianal fistulae. Clinically relevant reductions in draining fistulae were seen as early as Wk2 and maintained through Wk30.

Ultra-high-field sodium MRI as biomarker for tumor extent, grade and IDH mutation status in glioma patients

PurposeThis prospective clinical trial investigated sodium (23Na) MRI at 7 Tesla (T) field strength as biomarker for tumor extent, isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation in glioma patients. Methods28 glioma patients underwent 23Na MRI on a 7T scanner (Siemens Healthcare, Erlangen, Germany) parallel to standard 3T MRI before chemoradiation. Areas of Gadolinium-contrast enhancement (gdce), non-enhancing T2-hyperintensity (regarded as edema), necrosis, and normal-appearing white matter (nawm) were segmented on 3T MRI imaging and were co-registered with the 23Na images. The median total 23Na concentrations of all areas were compared by pairwise t-tests. Furthermore, areas of gdce and edema were merged to yield the whole tumor area without necrosis. Subsequently, the difference in median of the 23Na concentration of this whole tumor area was compared between IDH-mutated and IDH wild-type gliomas as well as MGMT methylated and MGMT not-methylated glioblastomas using Whitney-Mann U-tests. All p-values were corrected after the Bonferroni-Holm procedure. ResultsThe 23Na concentration increased successively from nawm to necrotic areas (mean ± sd: nawm = 37.84 ± 5.87 mM, edema = 54.69 ± 10.64 mM, gdce = 61.72 ± 12.95 mM, necrosis = 81.88 ± 17.53 mM) and the concentrations differed statistically significantly between all regarded areas (adjusted p-values for all pairwise comparisons < 0.05). Furthermore, IDH-mutated gliomas showed significantly higher 23Na concentrations than IDH wild-type gliomas (median [interquartile range]: IDH wild-type = 52.37 mM [45.98 – 58.56 mM], IDH mutated = 65.02 mM [58.87–67.05 mM], p = 0.039). Among the glioblastomas, there was a trend towards increased 23Na concentration in MGMT methylated tumors that did not reach statistical significance (median [interquartile range]: MGMT methylated = 57.59 mM [50.70 – 59.17 mM], MGMT not methylated = 48.78 mM [45.88 – 53.91 mM], p = 1.0). Conclusions23Na MRI correlates with the IDH mutation status and could therefore enhance image guidance towards biopsy sites as wells as image-guided surgery and radiotherapy. Furthermore, the successive decrease of 23Na concentration from central necrosis to normal-appearing white matter suggests a correlation with tumor infiltration.

Does the Diffusion Weighted Images and Subtration MRI of Hepatocellular Carcinoma has a Role in Predicting Outcome of Transarterial Chemoembolization?

AbstractBackground: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and has a poor prognosis unless treated. Ablative therapies are promising treatment options for patients who are not eligible for surgery.Aim of Study: Is to evaluate the predictive values of diffusion-weighted imaging (DWI) and Subtration MRI in evaluating the efficacy of transcatheter arterial chemoembol-ization (TACE) in treatment of patients with hepatocellular carcinoma (HCC).Patients and Methods: This study included 30 patients with pathologically proven HCC (38 HCC lesions) who were referred to the Radiology Department of Ain Shams University Hospitals and National Liver Institute, Menofiya University for post therapeutic assessment after transarterial hepatic chemoembolization. The study was carried on over a period of 12 month (from August 2017 to August 2018). Patients' ages ranged from 59 to 73 with a mean of age 59.6 years. Of the 30 patients only 6 were females and 24 were males.Results: We found that dynamic study is the gold standard in detection of recurrent lesions. Well defined nodular en-hancement, thick irregular marginal enhancement or gross enlargement of the lesion with arterial phase enhancement and contrast wash out were considered positive for malignancy. Ill-defined persistent enhancement or well defined rim marginal enhancement were considered benign post ablation changes. We found that subtraction technique was essential in differ-entiation between the normal hyperintense T1 signal of the ablation zone and arterial enhancement of the lesion. The high signal intensity seen in T1 images post TACE was explained by haemorrhagic coagulative necrosis. Subtraction imaging is ideally suited for such a role where the unenhanced T1-weighted sequence is subtracted from the identical contrast enhanced sequence.Conclusion: We conclude that in evaluation of HCC after TACE, ADC calculated at DWI had weaker correlation to tumor necrosis degree than did findings with subtraction contrast-enhanced MRI. However, there was no difference between both methods in diagnosis of complete tumor necrosis.We suggest that whenever possible, gadolinium contrast enhancement and subtraction imaging be used for assessment of tumor necrosis after TACE.