T1 Hypointense Research Articles

Comparison of MRI findings for predicting massive hemorrhage during cesarean section in patients with placental malposition: partial placental volume of lower uterine segment is an accurate and objective indicator.

To comprehensively compare the diagnostic ability and inter-reader agreement of magnetic resonance imaging (MRI) findings for predicting massive hemorrhage after cesarean section in patients with placental malposition, aiming to identify the most reliable and objective indicators. Totally, 148 consecutive patients with placental malposition underwent MRI and cesarean section at our hospital between January 2014 and July 2021. The patients were divided into massive and non-massive hemorrhage groups. MRI findings of placenta accreta, placental position, and placental volume were evaluated by two radiologists, and inter-reader agreement was calculated. Diagnostic ability for predicting massive hemorrhage was evaluated using receiver operating characteristic analysis. Intraplacental T2 dark bands (100% vs.58.2%, p = 0.001), placental bulge (50% vs. 3.7%, p < 0.001), loss of retroplacental T2 hypointense line (100% vs. 67.2%, p = 0.01), myometrial thinning (92.9% vs. 57.5%, p = 0.009), total placenta previa (64.3% vs. 23.9%, p = 0.033), and anterior placenta (35.7% vs. 10.5%, p = 0.02) were significantly observed in massive hemorrhage group. Partial placental volume of lower uterine segment (PVpartial) was larger in massive hemorrhage group (166 [108-214] cm3 vs. 70 [43-112] cm3 p < 0.001), had the second highest intraclass correlation coefficient (0.84), and had the highest area under the curve (0.81) for diagnosing massive hemorrhage. This study revealed PVpartial is an accurate and objective indicator for massive hemorrhage, independent of radiologists' experience. This indicator potentially enables prediction of massive hemorrhage, improving pre-operative planning in high-risk pregnancies.

Genetic spectrum of neuronal ceroid lipofuscinosis & its genotype-phenotype correlation -A single centre experience of 56 cases.

Neuronal ceroid lipofuscinoses (NCLs) are progressive, autosomal recessive lysosomal storage disorders primarily affecting children, marked by seizures, cognitive decline, motor regression, and visual impairment. Limited genetic data exist for South Asian populations, with most studies relying on enzymatic assays or electron microscopy. This study explores the genetic spectrum of NCL and genotype-phenotype correlations in a cohort from South India. A retrospective analysis was conducted on 56 genetically confirmed NCL patients diagnosed between January 2018 and June 2024 at a specialized neurological center in South India. Genetic analysis using next-generation sequencing (NGS) were performed, with variants classified as per ACMG guidelines. Clinical, electroencephalographic (EEG), imaging, and electron microscopy (EM) findings were reviewed, and genotype-phenotype correlations were analyzed. The cohort (33 males, 23 females) had a median age of onset of 36 months and a median disease duration of 65.5 months. Eight genetic subtypes were identified, with predominant mutations in TPP1 (19.64%), CLN6, MFSD8, and CLN8 (16.07% each). Seizures (75%), regression of milestones (87.5%), visual impairment (33.9%), and ataxia (57.1%) were common. EEG abnormalities were found in 76.3%, MRI revealed cerebellar atrophy in 89.13%, and thalamic T2 hypo-intensity in 91.3%. EM showed curvilinear and fingerprint profiles. Of the identified variants, 31 were previously reported, while 29 were novel. This is the largest single-center NCL cohort in South Asia, highlighting a diverse genetic spectrum and significant novel variants, underscoring the importance of genetic testing for diagnosis and future therapies.

Image characteristics of retained medullary cord in secondary neurulation arrest: an observational study

Retained medullary cord (RMC) is a recently defined term denoting closed spinal dysraphism arising from the failure of regression in secondary neurulation. Despite the acknowledgment of this condition, there needs to be more literature elucidating the radiologic manifestations of RMC. This study aimed to describe the MR imaging findings of RMC. A retrospective analysis was conducted on spinal MRI scans of pediatric patients with surgically confirmed RMC, from January 2014 to August 2023. The investigation focused on evaluating the following image characteristics: level and morphology of the cord-like structure (C-LS), the signal intensity in the far distal C-LS, nerve root-like structures originating from the C-LS, intradural fatty lesions, and arachnoid cysts. This study included 38 patients (19 girls, mean age 7.3 months) who showed a low-lying cord in all cases. The morphology of C-LS was either smooth tapered (50%) or hourglass with fusiform cystic dilatation (50%). The C-LS exhibited aberrant T2 hypointense signal compared to the juxta-proximal level. T2 hypointense signal vestigial nerves emanating from the C-LS and intradural fatty masses were observed (89.5%). Sacral arachnoid cysts in extradural location were identified in eight patients. The characteristic MR features of RMC revealed an extremely low-lying distal C-LS with smooth tapering or hourglass-shaped cystic dilatation of the caudal part, accompanied by an intradural fatty stalk and the aberrant signal vestigial nerve. This study suggests those radiologic findings can be RMC instead of the previously called terminal syrinx with low-lying conus.

Magnetic resonance imaging characteristics of ovarian torsion: insights into diagnostic features.

We aimed to describe the magnetic resonance imaging (MRI) features of adnexal torsion, additional radiological findings and apparent diffusion coefficient (ADC) measurements of the affected and non-affected ovaries. We retrospectively examined the MRI of 34 torsed adnexa of 34 cases. We specifically examined the peripherally displaced follicle sign, stromal edema, lack of stromal contrast enhancement, follicular rim sign, T2 hypointense rim sign, uterine deviation, adnexal displacement, whirlpool sign, T2 hypointense dot sign, and tubal thickening. These signs were systematically compared between the torsed and non-torsed adnexa. In addition to that, the presence of free fluid was recorded. As a quantitative analysis, ovarian size and stromal ADC values in torsed and non-torsed ovaries were measured. The average age was 36.6years. The right ovary was torsed in 21 (61.8%) of the cases, and the left ovary was torsed in 13 (38.2%). There were significant differences between groups in all signs except the follicular rim sign. The highest accuracy was at the whirlpool sign (0.93). This was followed by uterine deviation and stromal edema (0.85). The accuracy rates of other findings are, respectively, lack of stromal contrast enhancement (0.81), T2 hypointense dot sign (0.79), peripherally displaced follicle sign (0.77), displacement of the adnexa (0.66), tubal thickening (0.66), T2 hypointense rim sign (0.62) and follicular rim sign (0.54). The largest size of ovary in patients with torsion was significantly larger, with an average of 67.5 ± 16.3mm, compared to 38.8 ± 7.7mm in non-torsed adnexa (p < 0.001). Additionally, the stromal ADC value was significantly higher in torsed ovarian stroma, averaging 1930.5 ± 455.4 (10⁻⁶ mm2/s) compared to 1655.7 ± 349.3 (10⁻⁶ mm2/s) in non-torsed ovarian stroma (p < 0.001). In our study, we conducted a comprehensive evaluation of various imaging signs associated with adnexal torsion. The most reliable indicators of adnexal torsion, based on their high accuracy rates, include an enlarged ovary, the presence of the whirlpool sign, uterine deviation, and stromal edema.

SURG-42. THE T1/T2 RATIO IS ASSOCIATED WITH RESECTABILITY IN PATIENTS WITH IDH-MUTANT ASTROCYTOMAS CNS WHO GRADES 2 AND 3

Abstract PURPOSE IDH-mutant astrocytomas CNS WHO grade 2 and 3 show heterogenous appearance on magnetic resonance imaging (MRI). In the pre-molecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival in patients with IDH-mutant astrocytomas. METHODS Patient data from two centers (Center A: Sahlgrenska University Hospital, Gothenburg, Sweden; Center B: LMU University Hospital, Munich, Germany) were collected retrospectively. Inclusion criteria were as follows: pre- and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003-2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and overall survival. RESULTS The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median overall survival was 134 months and did not differ between the cohorts (p=0.29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 versus 4.6 cm3, p=0.03). The median extent of resection in these patients was 65% versus 90% (p=0.03). The ratio itself did not correlate with overall survival. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (HR 1.02, 95% CI 1.01-1.03, p&amp;lt;0.01). CONCLUSION The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.

Gadoxetic acid-enhanced MRI for the detection of liver metastases from melanoma.

We aimed to assess imaging findings and detection sensitivity for melanoma liver metastases on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study included patients with melanoma liver metastasis who underwent gadoxetic acid-enhanced MRI. Two abdominal radiologists independently evaluated signal characteristics of liver metastases on morphologic imaging (precontrast T1- and T2-weighted imaging), diffusion-weighted imaging (DWI), dynamic imaging, and hepatobiliary phase (HBP). Imaging findings were compared according to detection on HBP and the primary site of the melanoma using logistic regression with the generalized estimating equation (GEE). Detection sensitivity for metastases was compared among different MR imaging sets using logistic regression with GEE. A total of 67 patients with 254 liver metastases were included (44 women; mean age ± standard deviation, 65.6 ± 13.0 years). On HBP, 76.0% of metastases were detected, and 55.5% (141/254) showed hypointensity. Most of the metastases that were not detected on HBP originated from ocular melanomas (98.4%, 60/61), ≤1 cm (90.2%, 55/61) and showed T1 hyperintensity (98.4%, 60/61). Metastases from non-ocular melanomas more frequently showed T1 hypointensity, T2 hyperintensity, diffusion restriction, arterial enhancement, and HBP hypointensity than those from ocular melanomas (Ps ≤ 0.019). The detection sensitivity of HBP (76.0%) was significantly higher than DWI (65.7%, P = 0.006), but lower than morphologic imaging (98.8%, P < 0.001) and dynamic imaging (97.6%, P < 0.001). The detection sensitivity of HBP for melanoma liver metastasis was 76.0%, which was lower than that of morphologic or dynamic imaging. HBP of gadoxetic acid-enhanced MRI has little advantage in detecting melanoma liver metastases.

8194 Extramedullary Hematopoiesis Involving Bilateral Adrenal Glands In A Patient With Sickle Cell Anemia

Abstract Disclosure: V.T. Pham: None. L.N. Sendos: None. Title: Extramedullary hematopoiesis involving bilateral adrenal glands in a patient with sickle cell anemia Background: Extramedullary hematopoiesis refers to blood cell production occurring outside the bone marrow. It is a reactive process caused by inadequate production or excessive destruction of blood cells typically seen in patients with hereditary anemias or infiltrative bone marrow disorders. Extramedullary hematopoiesis usually occurs in the spleen, liver and lymph nodes, but it can also very rarely arise from the adrenal glands. Case Presentation:We present a case of a 42-year-old male with a history of sickle cell anemia who presented with chest pain and shortness of breath and had a chest CT angiography which incidentally showed a 5.6 x 3.8 cm left adrenal mass and a 2.9 x 2.1 cm right adrenal mass. Further evaluation with an MRI abdomen with and without contrast revealed a 5.5 cm lobulated left adrenal mass with patchy areas of microscopic fat and faint delayed heterogeneous enhancement as well as a 2.2 cm right adrenal nodule. The nodules were described as markedly T2 hypointense with heterogeneous T1 hyperintense/isointense signal on MRI with a broad differential diagnosis including extramedullary hematopoiesis in bilateral adrenal glands, lipid poor adenoma or neoplasm. Regarding his sickle cell disease history, the patient was diagnosed as an infant and had very rare episodes of sickle cell pain crisis as a child. However, once he entered adulthood, he began to have multiple episodes of sickle cell pain crisis requiring hospitalizations and transfusions. On further review of patient’s prior imaging scans during these previous hospitalizations, he was first noted to have bilateral sub centimeter adrenal nodules on a CT Abdomen without contrast done almost a decade prior to his current presentation. We ordered biochemical evaluation which did not show any evidence of adrenal hormonal hypersecretion. His case was discussed at our multidisciplinary conference with the radiology and surgery team and it was concluded that the imaging characteristics were most consistent with extramedullary hematopoiesis in the setting of bilateral adrenal gland involvement and patient’s history of sickle cell anemia. Therefore, no immediate surgical resection was recommended. Given the size of the left adrenal mass being greater than 4 cm in size, we advised follow-up imaging for surveillance. Discussion:There has been a rise in detection of adrenal incidentalomas due to the increased use of advanced diagnostic imaging in healthcare settings. When patients with hematologic diseases are found to have adrenal incidentalomas, it is important to consider extramedullary hematopoiesis in the differential diagnosis to avoid unnecessary invasive procedures and surgeries. Presentation: 6/2/2024

6797 Pituitary Apoplexy as initial Presentation of IgG4-Related hypophysitis

Abstract Disclosure: M. Alameri: None. A. Alnuaimi: None. Introduction: IgG4-related hypophysitis is a rare disease due to IgG4 lymphoplasmacytic infiltration of the pituitary gland. It can either be isolated or part of a multisystemic disease. We report a rare case of pituitary apoplexy as first manifestation of IgG4-RD. Case report: A 27-year-old previously healthy male presented to emergency department with severe headache, nausea, vomiting and visual impairment. CT brain showed a large sellar suprasellar mass of 3cm with thick rim enhancement. Blood test showed evidence of central adrenal insufficiency, central hypothyroidism and secondary hypogonadism. Patient was started on hormone replacement therapy for central adrenal insufficiency and central hypothyroidism. Pituitary magnetic resonance imaging (MRI) demonstrated a 3.1 x 2.4 x 2.4 cm well-defined large sellar suprasellar mass with thick rim enhancement with intrinsic heterogeneous T2 signal with hypointense T1 signal on fat-suppressed post contrast imaging consistent with necrotic haemorrhagic suggestive of pituitary apoplexy and background of hypophysitis. Upward displacement of optic chiasm was noted without involvement of cavernous sinus. The patient was initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, eventually, he underwent transsphenoidal surgery due to alternated level of consciousness. Pituitary histopathology showed that vast majority of the tissue is necrotic. A small fragment of viable anterior pituitary tissue is present, which measures up to 5.5 mm in greatest dimension which exhibited marked chronic inflammation, predominantly comprised of small lymphocytes. Plasma cells were present and staining with IgG/IgG4 revealed two high-power fields with clusters of approximately 25 and 50 IgG4 positive plasma cells, respectively. Blood test showed elevated blood IgG4 levels of &amp;gt;2.60 g/L (normal reference range 0.03-2.01 g/L). Case was discussed at Endocrine MDT meeting which agreed that blood tests result along with histopathology findings were in keeping with IgG4-Related hypophysitis as per the Mayo Clinic, Leporati and Japan-Korea proposed criteria. Because blood IgG4 levels were elevated, a systemic evaluation was performed. No evidence of other systemic disease found. High dose steroid therapy was initiated, which reduced remnant inflammatory sellar changes. Discussion and conclusion: IgG4-related pituitary disease should be considered as differential diagnosis in unusual presentations of pituitary apoplexy in the context of sellar suprasellar hypophysitis. Presentation: 6/2/2024

Unusual MRI abnormality in patients with nonketotic hyperglycaemia-associated seizures

Abstract Nonketotic hyperglycaemia (NKH) is a metabolic disorder typically observed in individuals with inadequately managed or undiagnosed diabetes mellitus (DM). Seizures are a common clinical presentation in NKH, and they tend to respond better to glucose correction than anticonvulsant therapy. MRI scans may reveal both subcortical T2/fluid-attenuated inversion recovery (FLAIR) imaging hypointensity and cortical changes, including cortical grey matter T2/FLAIR imaging hyperintensity and cortical or leptomeningeal enhancement, although cortical abnormalities are less frequently observed. These alterations are reversible when the underlying metabolic disturbance is effectively addressed. We suggest the role of iron accumulation as a mechanism for subcortical T2 hypointensity using T2* weighted imaging. Our cases substantiate the significance of subcortical T2/FLAIR hypointensity as a fundamental feature of this condition. In the appropriate clinical context, the recognition of these MRI abnormalities can help prevent misdiagnosis and facilitate timely treatment.

Differentiation of bacterial orbital cellulitis and diffuse non-specific orbital inflammation on magnetic resonance imaging.

To examine the radiological differences between bacterial orbital cellulitis (OC) and diffuse non-specific orbital inflammation (DNSOI) on magnetic resonance imaging (MRI). Retrospective study of patients with OC and DNSOI with an MRI orbital scan. Localised orbital inflammation (e.g., idiopathic dacryoadenitis and myositis), quiescent orbital inflammation and pre-septal cellulitis were excluded. Thirty-two patients presenting between 2008 and 2023, including twenty-one OC patients (mean age: 42.5 ± 24.9 years old, male: 6), and eleven DNSOI patients (mean age: 52.3 ± 17.8 years old, male: 16). Both OC and DNSOI demonstrate orbital fat contrast-enhancement. However, whilst OC demonstrated a hyperintense T2 signal (P < 0.001), variable signal was observed in DNSOI, with a hypointense T2 signal more suggestive of DNSOI (P = 0.012). When the lacrimal glands were involved, indistinct margins were more likely in OC (P < 0.001), whilst gross enlargement and contrast-enhancement was observed in DNSOI (P = 0.032 and 0.017, respectively). Peripheral contrast-enhancement of the extraocular muscle (EOM) (P = 0.002) was more common in OC, whilst DNSOI demonstrated variable contrast-enhancement throughout the affected EOM (P < 0.001). The presence of contralateral abnormalities, such as lacrimal gland enlargement and EOM involvement, are more suggestive of DNSOI. Several MRI features, beyond overt sinogenic disease, may help to differentiate OC from DNSOI, including the orbital fat signal intensity, EOM and/or lacrimal gland involvement, and contralateral orbital abnormalities. However, these features may not be specific, and thus highlights the ongoing radiological dilemma clinicians are faced when tasked with differentiating between infectious and non-infectious orbital inflammatory disease.

Gadoxetate disodium (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging for differentiation between benign and malignant splenic lesions in dogs.

Malignant splenic lesions in dogs are common, with hemangiosarcoma diagnosed most frequently, and there have been no consistent clinicopathologic, gross, or imaging characteristics identified that differentiate malignant from benign splenic lesions. Histopathology is required for definitive diagnosis, and given the poor long-term prognosis of malignant splenic lesions, a noninvasive tool to aid in diagnosis would be valuable. This prospective cohort study utilized gadoxetate disodium, a liver-specific contrast agent (Gd-EOB-DPTA; Eovist), to identify the general lesion and pre- and postcontrast signal characteristics of benign and malignant splenic and hepatic lesions in dogs with naturally occurring disease. Twenty-five dogs were enrolled, Eovist-enhanced MRI was performed, and dogs were taken to surgery for splenectomy and other organ biopsy. All histopathology and MRI studies were evaluated by a single pathologist and a single radiologist, respectively. The associations between the tumor type and numerous variables defined on MRI were evaluated using Fisher's exact tests, and the significance was identified at a P-value of.05. Malignant splenic masses were identified in 11/25 (44%) dogs, and 5/11 malignancies represented hemangiosarcoma. The presence of abdominal effusion (P=.017) and the presence of hepatic nodules on MRI (P=.009) were associated with splenic malignancy. There were no benign T2 hyperintense and no malignant T2 hypointense lesions (P=.021). Utilization of the T2 W MRI sequence may aid in the identification of malignant splenic lesions, particularly when accompanied by abdominal effusion and hepatic lesions.

Disability independent of cerebral white matter demyelination in progressive multiple sclerosis

The pathogenic mechanisms contributing to neurological disability in progressive multiple sclerosis (PMS) are poorly understood. Cortical neuronal loss independent of cerebral white matter (WM) demyelination in myelocortical MS (MCMS) and identification of MS patients with widespread cortical atrophy and disability progression independent of relapse activity (PIRA) support pathogenic mechanisms other than cerebral WM demyelination. The three-dimensional distribution and underlying pathology of myelinated T2 lesions were investigated in postmortem MCMS brains. Postmortem brain slices from previously characterized MCMS (10 cases) and typical MS (TMS) cases (12 cases) were co-registered with in situ postmortem T2 hyperintensities and T1 hypointensities. T1 intensity thresholds were used to establish a classifier that differentiates MCMS from TMS. The classifier was validated in 36 uncharacterized postmortem brains and applied to baseline MRIs from 255 living PMS participants enrolled in SPRINT-MS. Myelinated T2 hyperintensities in postmortem MCMS brains have a contiguous periventricular distribution that expands at the occipital poles of the lateral ventricles where a surface-in gradient of myelinated axonal degeneration was observed. The MRI classifier distinguished pathologically confirmed postmortem MCMS and TMS cases with an accuracy of 94%. For SPRINT-MS patients, the MRI classifier identified 78% as TMS, 10% as MCMS, and 12% with a paucity of cerebral T1 and T2 intensities. In SPRINT-MS, expanded disability status scale and brain atrophy measures were similar in MCMS and TMS cohorts. A paucity of cerebral WM demyelination in 22% of living PMS patients raises questions regarding a primary role for cerebral WM demyelination in disability progression in all MS patients and has implications for clinical management of MS patients and clinical trial outcomes in PMS. Periventricular myelinated fiber degeneration provides additional support for surface-in gradients of neurodegeneration in MS.

Intraventricular presentation of Rosai–Dorfman disease: a case report with review of literature

BackgroundRosai–Dorfman disease (RDD)/sinus lymphohistiocytosis is a rare benign lymphoproliferative disorder. Only 25% show extra-nodal manifestation, only 5% are seen involving the CNS, with intraventricular manifestation rarely reported. Our aim was to highlight important imaging features which would be useful in considering this entity as one of the differentials while encountering this rare entity.Case descriptionWe present a case of a 34-year-old female with complaints of headache, altered behavior and visual disturbances. MRI brain showed T2 hypointense lesion arising from the left choroid plexus with dense homogenous enhancement, with multiple additional extra-axial dural-based lesions and a small lesion involving right choroid plexus. Left parietal craniotomy was done, and the lesion was excised. Histopathology showed large foamy macrophages in eosinophilic background, with lymphophagocytosis (emperipolesis), confirming the diagnosis of Rosai–Dorfman disease.ConclusionsIntraventricular Rosai–Dorfman disease is a rare entity. Imaging features of T2 hypointense homogenously enhancing lesion with blooming on GRE, without features of calcification or hemorrhage, may be helpful in prompting adequate histopathologic evaluation.

An Algorithmic Approach to MR Imaging of Hypomyelinating Leukodystrophies.

Hypomyelinating leukodystrophies (HLDs) are a heterogeneous group of white matter diseases characterized by permanent deficiency of myelin deposition in brain. MRI is instrumental in the diagnosis and recommending genetic analysis, and is especially useful as many patients have a considerable clinical overlap, with the primary presenting complains being global developmental delay with psychomotor regression. Hypomyelination is defined as deficient myelination on two successive MR scans, taken at least 6 months apart, one of which should have been obtained after 1 year of age. Due to subtle differences in MRI features, the need for a systematic imaging approach to diagnose and classify hypomyelinating disorders is reiterated. The presented article provides an explicit review of imaging features of a myriad of primary and secondary HLDs, using state of the art genetically proven MR cases. A systematic pattern-based approach using MR features and specific clinical clues is illustrated for a quick yet optimal diagnosis of common as well as rare hypomyelinating disorders. The major MR features helping to narrow the differential diagnosis include extent of involvement like diffuse or patchy hypomyelination with selective involvement or sparing of certain white matter structures like optic radiations, median lemniscus, posterior limb of internal capsule and periventricular white matter; cerebellar atrophy; brainstem, corpus callosal or basal ganglia involvement; T2 hypointense signal of the thalami; and presence of calcifications. The authors also discuss the genetic and pathophysiologic basis of HLDs and recent methods to quantify myelin in vivo using advanced neuroradiology tools. The proposed algorithmic approach provides an improved understanding of these rare yet important disorders, enhancing diagnostic precision and improving patient outcomes. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Efficacy and safety of peginterferon beta-1a compared to interferon beta-1a in relapsing remitting multiple sclerosis patients: A phase 3, randomized, non-inferiority clinical trial (PEGINTEGRITY)

BackgroundMultiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients. MethodsThis study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments. ResultsA total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes. ConclusionThe results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS.This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133).

Very-long T2-weighted imaging of the non-lesional brain tissue in multiple sclerosis patients.

The purpose of this study is to demonstrate that T2-weighted imaging with very long echo time (TE > 300 ms) can provide relevant information in neurodegenerative/inflammatory disorder. Twenty patients affected by relapsing-remitting multiple sclerosis with stable disease course underwent 1.5T 3D FLAIR, 3D T1-weighted, and a multi-echo sequence with 32 echoes (TE = 10-320 ms). Focal lesions (FL) were identified on FLAIR. T1-images were processed to segment deep gray matter (dGM), white matter (WM), FL sub-volumes with T1 hypo-intensity (T1FL), and dGM volumes (atrophy). Clinical-radiological parameters included Expanded Disability Status Scale (EDSS), disease duration, patient age, T1FL, and dGM atrophy. Correlation analysis was performed between the mean signal intensity (SI) computed on the non-lesional dGM and WM at different TE versus the clinical-radiological parameters. Multivariable linear regressions were fitted to the data to assess the association between the dependent variable EDSS and the independent variables obtained by T1FL lesion load and the mean SI of dGM and WM at the different TE. A clear trend is observed, with a systematic strengthening of the significance of the correlation at longer TE for all the relationships with the clinical-radiological parameters, becoming significant (p < 0.05) for EDSS, T1FL volumes, and dGM atrophy. Multivariable linear regressions show that at shorter TE, the SI of the T2-weighted sequences is not relevant for describing the EDSS variability while the T1FL volumes are relevant, and vice versa, at very-long TEs (around 300 ms); the SI of the T2-weighted sequences significantly (p < 0.05) describes the EDSS variability. By very long TE, the SI primarily originates from water with a T2 longer than 250 ms and/or free water, which may be arising from the perivascular space (PVS). Very-long T2-weighting might detect dilated PVS and represent an unexplored MR approach in neurofluid imaging of neurodegenerative/inflammatory diseases.

Hypothalamic Hamartoma in an 11-Year-Old Female: Clinical Presentation, Diagnostic Evaluation, and Management Strategies – A Case Report and Literature Review

Background: Hypothalamic hamartomas (HH) are rare, benign brain tumors that can cause severe neurological symptoms, including epilepsy. This report presents a case of an 11-year-old female with HH, highlighting the clinical presentation, diagnostic workup, and management strategies. Case Presentation: An 11-year-old female with no prior medical history presented with generalized tonic-clonic seizures during sleep, characterized by convulsions, cyanosis, tongue biting, frothing at the mouth, and loss of consciousness lasting 1-2 minutes. Subsequent episodes included focal Jacksonian seizures involving the face and right eye myoclonus, progressing to generalized convulsions. Neurological examination and development were normal, with no family history of epilepsy. MRI revealed a sessile lesion in the left hypothalamus with T2/FLAIR hyperintensity and T1 hypointensity. Laboratory tests, including thyroid function, gynecological ultrasound, and various blood tests, were normal. A 48-hour video EEG indicated sensorimotor cortex involvement in both hemispheres, likely linked to the hypothalamic lesion. Management: Initial management involved observation without antiepileptic medications. Due to persistent seizures, the treatment plan included oxcarbazepine, titrated to 1200 mg/day, and Keppra (levetiracetam) 1000 mg/day. Efforts were made to discontinue Keppra and maintain monotherapy with oxcarbazepine. Given the small size of the lesion and effective seizure control with medication, surgical intervention was not pursued. Conclusion: This case underscores the importance of comprehensive diagnostic evaluation and individualized treatment plans for patients with HH. While medical management can be effective for small lesions, surgical options reported in the literature provide alternative strategies for larger or treatment-resistant cases. A multidisciplinary approach is crucial in managing the complex presentation of HH to optimize patient outcomes and improve quality of life.

The T1/T2 Ratio is Associated With Resectability in Patients With Isocitrate Dehydrogenase-Mutant Astrocytomas Central Nervous System World Health Organization Grades 2 and 3.

Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas. Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS. The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 vs 4.6 cm3, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01). The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.

IMG-07. PEDIATRIC CRANIAL INCIDENTALOMAS: A SYSTEMATIC REVIEW UTILIZING MACHINE LEARNING

Abstract BACKGROUND The use of diagnostic neuroimaging in the care of pediatric patients continues to increase, leading to a rise in incidentally discovered lesions. The understanding of appropriate assessment and management of these findings is critical to providing comprehensive and timely care. This review aims to analyze the current literature to characterize diagnostic and prognostic characteristics of incidentally found brain tumors in pediatric patients. METHODS Using the guidelines under the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), Pubmed and Medline (NCBI) databases were searched using selected keyword combinations and machine learning-assisted software. Case reports, case series, and retrospective cohort studies published up to December 2023 were included. RESULTS A total of 20 studies encompassing 627 patients were included in the review. The most common indications for imaging were headache (204; 33%), seizures (96; 15%), and trauma (78; 12%). Of studies providing information regarding localization, lesions were found in the supratentorial region in 327 (52%) cases and infratentorial region in 190 (30%). Of studies reporting imaging characteristics, T1 hypointensity (183/302; 61%), T2 hyperintensity (410/497; 82%), and no contrast enhancement (58/97; 60%) were the most common findings. Four hundred and thirty (68%) patients were observed after diagnosis, 83 (13%) patients underwent surgical intervention at diagnosis, and 40 (6%) patients underwent surgery after observation. Of 91 patients with histopathology data available, pilocytic astrocytoma (19; 21%) was most commonly reported. CONCLUSION In this study, we provide a review of diagnostic characteristics of incidentally discovered brain tumors in the pediatric population. Management of such lesions has changed greatly over the past several decades, and risks of surgical intervention should be weighed against a more conservative management and interval monitoring approach. These results may help guide discussions regarding disclosure of findings and recommendations for additional clinical management.

IMMU-04. THE ROLE OF CHECK POINT INHIBITORS IN PEDIATRIC PRIMARY DIFFUSE LEPTOMENINGEAL MELANOMATOSIS: REPORT OF TWO CASES

Abstract BACKGROUND Primary diffuse leptomeningeal melanomatosis (PDLM), a subtype of malignant melanomas of CNS, is rare, especially in children. PDLM is defined by diffuse invasiveness of the leptomeninges with or without nodules. Clinical manifestations of PDLM are nonspecific, mimicking the diagnosis of meningitis. As PDLM is neither sensitive to chemotherapy nor radiotherapy, the prognosis is extremely poor. Recently, some new therapeutic aspects like immunotherapy, especially immune check point inhibitors (ICI) are emerging. Cases report: First case: A 13 years old boy presented with 4 months of weakness, dysphasia and vomiting. MRI demonstrated diffuse leptomeningeal enhancement of the brain and spine. Brain biopsy confirmed the diagnosis of PDLM, with low PDL1 stains in immunohistochemistry, without targetable alterations on NGS. PET FDG normal. Treatment with ICI (Nivolumab 1 mg/kg/dose and Ipilimumab 3 mg/kg/dose, 4 courses every 21 days) was started. He developed severe complications after the 1st course (ICI enterocolitis, pancreatitis) and progressive disease after 2 courses. Craniospinal radiotherapy was delivered at a dose of 30 Gy. The disease continued to progress; the patient died nine months after diagnosis. Second case: A 7-year-old boy presented with diplopia, headache and vomiting. MRI demonstrated a cranial leptomeningeal enhancement and hypo-intense T1 and hyper-intense T2 signal at bilateral medial frontal cortex area. PET FDG normal. Brain biopsy confirmed the diagnosis of PDLM, with TMB 1.9, NRAS mutation and wild type BRAF by NGS. He started combination of ICI therapy. Three weeks after 1st course of Ipilimumab-Nivolumab he was admitted to PICU with prolonged status epilepticus. MRI demonstrated progression of leptomeningeal disease. Trametinib was deferred by parents and the child succumbed a year from diagnosis. CONCLUSIONS We report two cases of pediatric patients with PDLM treated unsuccessfully by immune check point inhibitors, emphasizing the diagnostic and therapeutic challenges in such a rare disease.