Negative Magnetic Resonance Imaging Research Articles

7594 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

9272 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery

Abstract Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None. Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation. Presentation: 6/1/2024

Comparison of the Effectiveness of Computed Tomography and Magnetic Resonance Imaging Techniques in Patient Groups Aged under and over 65 Years and Diagnosed with Ischemic Stroke in the Emergency Department

Objectives: Stroke is a condition with high morbidity and mortality. This study aims to investigate whether the effectiveness of Computed Tomography (CT) and diffusion-weighted Magnetic Resonance Imaging (MRI), the techniques that have a significant place in the diagnosis of ischemic stroke, the most common form of stroke, are affected by the physiological changes of advanced age. Methods: A total of 436 patients were included in the study. The study population was divided into two groups depending on age: those above 65 and those under 65. Medical files, both the emergency department and clinical ward files, of the patients who were admitted to the emergency department in nine months and admitted to the neurology clinic with the diagnosis of ischemic stroke were retrospectively analyzed. The time from admission to imaging was determined depending on patient files and the Hospital Management Information System (HBYS). The CT and MRI reports interpreted by radiologists were also reviewed. While recording the data, the presence of a lesion, its direction, and localization were also noted. Results: CT positivity was 21.3%, and the positivity of diffusion-weighted imaging was 82.1% in the study population. The time was shorter in the group of patients with positive CT results than in the group with negative CT results. In subjects under 65, the time between onset and imaging was shorter in the group with positive CT results than in the group with negative CT results. In subjects over 65, the time with positive CT results was not different from the group with negative CT results. It was determined that the mean time was shorter in the group with positive MRI results than in the group with negative results. In both the groups under the age of 65 and over the age of 65, the time interval was shorter in the patients with positive MRI results compared to those with negative MRI results. Conclusions: Regardless of the positivity or negativity of CT and MRI results, the mean time from symptom onset to imaging was shorter in the group under 65 years of age compared to the group over 65 years. Aging prolongs the time to admission and the neuroradiological response of geriatric patients.

Clinical impact of MRI on indeterminate findings on contrast-enhanced CT suspicious of HCC

Objectives In patients evaluated for hepatocellular carcinoma (HCC), magnetic resonance imaging (MRI) is often used secondarily when multiphase contrast-enhanced computed tomography (ceCT) is inconclusive. We investigated the clinical impact of adding MRI. Materials and methods This single-institution retrospective study included 48 MRI scans (44 patients) conducted from May 2016 to July 2023 due to suspicion of HCC on a multiphase ceCT scan. Data included medical history, preceding and subsequent imaging, histology when available, and decisions made at multidisciplinary team meetings. Results In case of possible HCC recurrence, 63% of the MRI scans were diagnostic of HCC. For 80% of the negative MRI scans, the patients were diagnosed with HCC within a median of 165 days in the suspicious area of the liver. In case of possible de-novo HCC in patients with cirrhosis, 22% of the scans were diagnostic of HCC and 33% of the negative MRI scans were of patients diagnosed with HCC within a median of 109 days. None of the non-cirrhotic patients with possible de-novo HCC and negative MRI scans (64%) were later diagnosed with HCC, but 3/5 of the indeterminate scans were of patients diagnosed with HCC in a biopsy. Conclusions Secondary MRI to a multiphase ceCT scan suspicious of HCC is highly valuable in ruling out HCC in non-cirrhotic patients and in diagnosing HCC non-invasively in cirrhotic patients and patients with prior HCC. Patients with cirrhosis or prior HCC are still at high risk of having HCC if MRI results are inconclusive or negative.

The genetic etiology is a relevant cause of central precocious puberty.

The etiology of central precocious puberty (CPP) has expanded with identification of new genetic causes, including the monogenic deficiency of Makorin-Ring-Finger-Protein-3 (MKRN3). We aimed to assess the prevalence of CPP causes and the predictors of genetic involvement in this phenotype. A retrospective cohort study for an etiological survey of patients with CPP from a single academic center. All patients with CPP had detailed medical history, phenotyping, and brain magnetic resonance imaging (MRI); those with negative brain MRI (apparently idiopathic) were submitted to genetic studies, mainly DNA sequencing studies, genomic microarray, and methylation analysis. We assessed 270 patients with CPP: 50 (18.5%) had CPP-related brain lesions (34 [68%] congenital lesions), whereas 220 had negative brain MRI. Of the latter, 174 (165 girls) were included for genetic studies. Genetic etiologies were identified in 22 patients (20 girls), indicating an overall frequency of genetic CPP of 12.6% (22.2% in boys and 12.1% in girls). The most common genetic defects were MKRN3, Delta-Like-Non-Canonical-Notch-Ligand-1 (DLK1), and Methyl-CpG-Binding-Protein-2 (MECP2) loss-of-function mutations, followed by 14q32.2 defects (Temple syndrome). Univariate logistic regression identified family history (odds ratio [OR] 3.3; 95% CI 1.3-8.3; P = .01) and neurodevelopmental disorders (OR 4.1; 95% CI 1.3-13.5; P = .02) as potential clinical predictors of genetic CPP. Distinct genetic causes were identified in 12.6% patients with apparently idiopathic CPP, revealing the genetic etiology as a relevant cause of CPP in both sexes. Family history and neurodevelopmental disorders were suggested as predictors of genetic CPP. We originally proposed an algorithm to investigate the etiology of CPP including genetic studies.

Genetic testing, another important tool in presurgical evaluation of focal epilepsies in childhood.

Epilepsy surgery may be a curative therapy for patients with drug-resistant epilepsies when focal lesions or foci are identified. Genetic testing is not yet routinely included in many presurgical evaluation programs although recent evidence support that finding a germline genetic mutation could help to better delineate the patient candidacy to surgery and provide valuable information on the expected surgery outcome. In this study, we report nine patients presenting drug-resistant focal epilepsy enrolled in presurgical evaluation. We show how the identification of genetic pathogenic variant in epilepsy known genes led to the interruption of the presurgical work-up and ruled out surgery in 7 of them. We observed that the co-existence of some recurrent clinical characteristics as early seizures' onset, frequent precipitating factors including fever, and developmental delay or intellectual disability may be useful markers for germline genetic pathogenic variants. In this group, genetic assessment should be mandatory during presurgical work up, mainly in patients with negative magnetic resonance imaging (MRI) or doubtful structural lesions. The integration of next generation targeted sequencing into the presurgical evaluation can improve the selection of candidates for resective surgery and fosters a personalized medicine approach with a better outcome. PLAINE LANGUAGE ABSTRACT: Genetic testing is not yet systematically included in the pre-surgical assessment of patients with drug-resistant focal epilepsies. In this study, through the description of nine patients, we underline how the integration of genomics into the presurgical work up can help in evaluating the patient candidacy to surgery and provide valuable information on expected surgery outcome.

Etiology and Diagnostic Challenges of Ulnar Wrist Pain in Pediatric and Adolescent Patients

Diagnosing the cause of ulnar-sided wrist pain can be difficult in the pediatric and adolescent age group. While frequently used, the diagnostic accuracy of magnetic resonance image (MRI), as compared with intraoperative arthroscopic findings, is not well-described in this population. This study aimed to determine concordance rates between magnetic resonance and arthroscopic findings depending on the specific ulnar wrist pathology. A retrospective review was performed to identify pediatric and adolescent patients who underwent operative treatment of ulnar wrist pain between 2004 and 2021. Patients were included in the analysis if they were <18 years of age, complained of ulnar-sided wrist pain, underwent MRI of the affected wrist with an available report interpreted by a consultant radiologist, and had a diagnostic arthroscopy procedure within one year of imaging. Ulnar pathologies analyzed included triangular fibrocartilage (TFCC) tears, ulnotriquetral (UT) ligament tears, lunotriquetral ligament abnormalities, and ulnocarpal impaction. A total of 40 patients with a mean age of 15-years-old (range 11 to 17) were included in the analysis. Twenty-four were female, and approximately half had their dominant extremity affected. Most had a history of antecedent trauma (n= 34, 85%), but only 15/40 (38%) had a history of fracture. The mean duration of symptoms prior to presentation was six months (standard deviation, 7). The most common etiologies were Palmer 1B TFCC tears (n= 27, 68%) followed by UT split tears (n= 11, 28%). MRI overall demonstrated high specificity (82% to 94%), but low sensitivity (14% to 71%) for ulnar-sided wrist conditions. Accuracy varied between 70% and 83% depending on the specific injury. While MRI is a useful adjunct for determining the cause of ulnar wrist pathologies, findings are often discordant when compared with diagnostic arthroscopy. Surgeons should have a high degree of suspicion for TFCC-related pathology in the setting of positive provocative clinical examination despite negative MRI findings in young patients. Diagnostic IIb.

Analysis of the performance of PET/CT using 18F-fluorodeoxyglucose in comparison with other diagnostic methods in drug-resistant epilepsy in children

Background. Epilepsy is one of the most common neurological diseases characterized by a persistent predisposition to epileptic seizures and the neurobiological, cognitive, psychological, and social consequences. In recent decades, despite the continuous development of antiepileptic drugs, there are still many patients with epilepsy that progresses to drug-resistant epilepsy. Currently, surgical treatment is one of the most important ways to treat such epilepsy. Collaboration between multidisciplinary teams and the combination of multiple neuroimaging methods are key to determining the exact localization of the epileptogenic zone. New diagnostic methods are being developed and the number of indications for their use is growing. The purpose of the study was to analyze the scientific literature on the effectiveness of positron emission tomography combined with computed tomography (PET/CT) using 18F-fluorodeoxyglucose compared to other diagnostic methods in drug-resistant epilepsy in children. Materials and methods. A literature search using keywords was conducted in Web of Science, Scopus, PubMed, and Elsevier databases. Results. Surgical treatment of drug-resistant epilepsy in children has become a specialized area in neurosurgery. Surgical removal or disconnection of a part of the brain, in which the epileptogenic zone is suspected, allows for a complete cure or a significant reduction in seizure frequency. It has been shown that a prerequisite for postoperative success is the accurate determination of the epileptogenic zone during a multistage preoperative diagnosis. Among many studies, nuclear medicine technologies play an important role in the presurgical examination of children with drug-resistant epilepsy. In combination with other methods, nuclear medicine helps identify the epileptogenic zone, especially in case of conflicting data, negative magnetic resonance imaging — negative epilepsy, focal cortical dysplasia or extratemporal lobe epilepsy. Single-photon emission CT and PET using functional neuroimaging with nuclear medicine indicators are classical methods and are recommended by neuroimaging specialists. In addition, one of the leading modern methods is PET/CT with 18F-fluorodeoxyglucose. It provides information that might be missed when using anatomical methods such as magnetic resonance imaging, and the area of hypometabolism detected with 18F-fluorodeoxyglucose PET/CT may be larger than the area of anatomical lesion detected on magnetic resonance imaging. Conclusions. For children with drug-resistant epilepsy, PET/CT using 18F-fluorodeoxyglucose is the most optimal method of preoperative diagnosis.

Pediatric cervical spine clearance after blunt trauma and negative CT: What is the role of MRI?

Background and purposeThe cervical spine in children has marked anatomical and biomechanical differences compared to adults, leading to significantly different patterns and incidence of spinal injury, and consequently to different X-ray and computed tomography (CT) imaging recommendations. Magnetic resonance imaging (MRI) has been validated to clear cervical spine trauma in adults, but not in pediatric patients. We hypothesized that MRI findings have a low probability to change management in children with spine trauma and negative CT findings. Materials and methodsWe reviewed records for admitted pediatric patients due to blunt trauma from January 2011 to May 2021, and identified 212 patients who underwent MRI within 3 days of a negative CT. Two neuroradiologists independently reviewed all CT and MRI images for the following categories: fracture, subluxation, spinal canal compromise, ligamentous injury, spinal canal hemorrhage, cord contusion and soft tissue hemorrhage. We identified follow-up MRI examinations as negative or positive for the above categories, and calculated the prevalence of each category as a percentage of cases with negative CT. We also evaluated whether negative and positive MRI groups differed significantly with respect to age and sex of the patients. Results and conclusionsIn our study of 212 children with cervical spine trauma and a negative CT, most follow-up MRI scans were found to be negative (79.9 %). Positive MRI findings consisted mainly of ligamentous sprain without disruption (15.1 %). Ligamentous disruption and epidural or soft tissue hemorrhage were found in 4.5 %, and focal cord contusion in 0.5 %. There was no statically significant difference between negative and positive MRI groups with respect to age (P = 0.45) and sex (P = 0.52). ConclusionIn our patient group with a negative CT, MRI did not significantly impact management nor contribute to cervical spine clearance in children.

Training in Cognitive Reappraisal Normalizes Whole-Brain Indices of Emotion Regulation in Borderline Personality Disorder

BackgroundBorderline personality disorder (BPD) is the prototypical disorder of emotion dysregulation. We have previously shown that patients with BPD are impaired in their capacity to engage cognitive reappraisal, a frequently employed adaptive emotion regulation strategy. MethodsHere, we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in patients with BPD. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 participants with BPD (14 female) and 22 healthy control participants (13 female) received training in psychological distancing and then completed a widely used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently defined patterns for negative affect and cognitive reappraisal implementation for each session. ResultsPatients with BPD showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. However, they did not show significant change in behavioral self-reports. ConclusionsTo our knowledge, this study represents the first longitudinal functional magnetic resonance imaging examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of patients with BPD.

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

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

Micro-ultrasound for the detection of clinically significant prostate cancer in biopsy-naive men with negative MRI.

Despite a negative magnetic resonance imaging (MRI), some patients may still harbor clinically significant prostate cancer (csPCa, Gleason grade group ≥2). High-resolution micro-ultrasound (microUS) is a novel imaging technology that could visualize csPCa that is missed by MRI. This retrospective review included 1011 consecutive patients biopsied between September 2021 and July 2023 in Alberta, Canada. Among them were 103 biopsy-naive patients with negative MRI (Prostate Imaging Reporting & Data System [PI-RADS] ≤2) undergoing microUS-informed prostate biopsy (n=56) scored using Prostate Risk Identification Using Micro-ultrasound (PRI-MUS) or standard transrectal ultrasound prostate biopsy (n=47). The primary outcome was detection rate of csPCa stratified by biopsy technique and PRI-MUS score. MicroUS biopsy identified csPCa in 14/56 (25%) compared to standard biopsy in 8/47 (17%) (p=0.33). Patients with lesions PRI-MUS ≥3 had csPCa detected at a higher rate compared to patients with PRI-MUS ≤2 (42% vs. 16%, p=0.03). The csPCa detection rate was significantly different comparing patients with prostate-specific antigen (PSA) density <0.15 and PRI-MUS ≤2 compared to patients with PSA density ≥0.15 and PRI-MUS ≥3 (14% vs. 60%, p=0.02). MicroUS may aid in the detection of csPCa for patients with negative MRI.

Rational Design of Magnetic Nanoparticles as T1-T2 Dual-Mode MRI Contrast Agents.

Magnetic nanoparticles (MNPs), either paramagnetic or superparamagnetic depending on their composition and size, have been thoroughly studied as magnetic resonance imaging (MRI) contrast agents using in vitro and in vivo biomedical preclinical studies, while some are clinically used. Their magnetic properties responsible in some cases for high magnetization values, together with large surface area-to-volume ratios and the possibility of surface functionalization, have been used in MRI-based diagnostic and theranostics applications. MNPs are usually used as positive (T1) or negative (T2) MRI contrast agents, causing brightening or darkening of selected regions in MRI images, respectively. This review focusses on recent developments and optimization of MNPs containing Gd, Mn, Fe and other lanthanide ions which may function as dual-mode T1-T2 MRI contrast agents (DMCAs). They induce positive or negative contrast in the same MRI scanner upon changing its operational mode between T1-weighted and T2-weighted pulse sequences. The type of contrast they induce depends critically on their r2/r1 relaxivity ratio, which for DMCAs should be in the 2-10 range of values. After briefly discussing the basic principles of paramagnetic relaxation in MNPs, in this review, the basic strategies for the rational design of DMCAs are presented and typical examples are discussed, including in vivo preclinical applications: (1) the use of NPs with a single type of contrast material, Gd- or Mn-based NPs or superparamagnetic NPs with appropriate size and magnetization to provide T2 and T1 contrast; and (2) inclusion of both types of T1 and T2 contrast materials in the same nanoplatform by changing their relative positions.

Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.

This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups. Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.

Predictive Factors for Extracapsular Extension of Prostate Cancer to Select the Candidates for Nerve-sparing Radical Prostatectomy.

Nerve-sparing radical prostatectomy (NSRP) for prostate cancer (PC) enables better postoperative recovery of continence and potency but may increase the risk of positive surgical margins. This study aimed to investigate preoperative predictive factors for extracapsular extension (ECE) of PC to select patients for NSRP. We retrospectively evaluated 288 patients with PC (576 lobes) diagnosed with 12-core transrectal ultrasound-guided biopsy and magnetic resonance imaging (MRI) who underwent laparoscopic or robot-assisted radical prostatectomy at our institution. Surgical specimens and preoperative parameters (prostate-specific antigen, prostate volume, biopsy and MRI findings, preoperative therapy) were analyzed. Of 576 prostate lobes, the incidence Ipsilateral ECE was identified in 97 (16.8%) lobes. The higher number of unilateral positive biopsy cores, the highest Gleason score 8 or more and positive unilateral findings on MRI are significant higher in prostate sides with ECE in univariate analysis. In multivariate analysis, positive unilateral MRI findings (odds ratio [OR], 2.86; p < 0.001) and unilateral biopsy positive core ≥ 3 (OR, 3.73; p < 0.001) were independent predictors of unilateral ECE. The detection rate of unilateral ECE in those cases with two factors (side-specific positive biopsy core 2 or less and side-specific MRI findings negative) was 7.1% (19/269). Patients with fewer unilateral positive biopsy cores and negative unilateral MRI findings might be good candidates for NSRP.

Repeated Prostate Cancer Screening Using Prostate-Specific Antigen Testing and Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has been proposed to enhance the benefit-to-harm ratio of prostate cancer screening, but data on repeated screening outcomes are lacking. To describe outcomes of prostate-specific antigen (PSA)-based screening with MRI and prostate biopsies at repeat screening. This secondary analysis examined the population-based, screen-by-invitation STHLM3-MRI randomized clinical trial, which recruited Swedish men aged 50 to 74 years. Men were eligible for repeat screening at 2 to 3 years if they had PSA levels of 1.5 ng/mL or greater at trial inclusion, were randomized to the MRI-targeted group (including screening using biomarkers and MRI), and were not diagnosed with prostate cancer after the first screening round. Repeat screening was performed between November 10, 2021, and February 20, 2023. Data analysis was performed between May and August 2023. Participants underwent blood sampling, including PSA testing. A biparametric MRI scan was performed if PSA levels were 3 ng/mL or greater, and men with lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or greater were referred for targeted and systematic biopsies. The primary outcome was clinically significant prostate cancer (Gleason score of ≥3 + 4). Secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score of 6), the number of elevated PSA tests, MRI scans, and biopsy procedures. Of 7609 men from the first screening round, 2078 (27.3%) were eligible for and were invited for rescreening. Among the invitees, 1500 (72.2%) participated. Their median age was 67 (IQR, 61-72) years. Of 1094 men with PSA levels between 1.5 and 2.9 ng/mL in the first screening round, 326 (29.8%) had levels of 3 ng/mL or greater in the second round. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater: 617 underwent MRI (92.5%), revealing 51 (7.6%) with equivocal lesions (PI-RADS score of 3) and 33 (4.9%) with suspicious lesions (PI-RADS score of ≥4). Only 10 of 383 men (2.6%) with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6. In this secondary analysis of the STHLM3-MRI randomized clinical trial, cancer detection during the second screening round in biennial PSA and MRI-based prostate cancer screening was limited, and the detection of low-grade tumors remained low. A substantial proportion of men exhibited elevated PSA levels during rescreening, and a considerable portion of MRI scans performed lacked lesions suggestive of cancer. Future studies should explore strategies to reduce MRI-related resource use. ClinicalTrials.gov Identifier: NCT03377881.

Clinical application of combination [11C]C-methionine and [13N]N-ammonia PET/CT in recurrent functional pituitary adenomas with negative MRI or [18F]F-FDG PET/CT

BackgroundWe assessed the value of positron emission tomography/computed tomography (PET/CT) with [13N]N-ammonia ([13N]N-NH3) and [11C]C-methionine ([11C]C-MET) for the evaluation and management of recurrent secreting pituitary adenoma, which could not be detected by magnetic resonance imaging (MRI) or fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET.MethodsNine consecutive patients with biochemical and clinical evidence of active recurrent tumor not detected by MRI and [18F]F-FDG PET were enrolled in this study. All of the patients underwent [13N]N-NH3 and [11C]C-MET PET/CT, after which the pattern of tracer uptake was studied, the tumor position was located, and a clinical decision was made.ResultsIn general, [11C]C-MET had a higher uptake in pituitary adenomas (PAs) than that in pituitary tissues, while [13N]N-NH3 had a higher uptake in pituitary tissue than in pituitary adenomas. Increased [11C]C-MET uptake was observed in all nine PAs and three pituitary tissues, while all pituitary tissues and only one pituitary adenoma showed increased [13N]N-NH3 uptake. Four patients had concordant imaging and surgical findings indicative of biochemical remission without hypopituitarism after treatment. Radiotherapy was adopted in two patients, medication in another two, and follow-up observation in one case.ConclusionCombined [11C]C-MET and [13N]N-NH3 PET/CT is effective in the differentiation of PAs from pituitary tissue in recurrent functional PAs with negative MRI or [18F]F-FDG PET. These results provide a valuable reference for further disease management.

Higher incidence of acute symptomatic seizures in probable antibody-negative pediatric autoimmune encephalitis than in major antibody-positive autoimmune encephalitis.

To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.

Sex-related differences in Cushing's disease: a systematic review and meta-analysis.

Cushing's disease is a rare endocrine disorder. This review aimed to examine sex-specific differences in Cushing's disease. A meta-analysis was performed on published articles discussing the gender impact of Cushing's disease. A systematic search was conducted to identify studies from Medline, Embase, CENTRAL and Scopus. Nine studies enrolling 1047 patients diagnosed with Cushing's disease were included in this meta-analysis. Male patients presented at a younger age (MD [mean difference]=-5.43; 95% CI [-5.78, -5.08]; P<.00001) than females. Male patients had a significantly higher prevalence of osteoporosis (RR [risk ratio]=1.75; 95% CI [1.36, 225]; P<.0001) and hypokalemia (RR=1.66; 95% CI [1.27, 2.16]; P=.0002). In addition, males had significantly higher rates of negative magnetic resonance imaging (RR=1.53; 95% CI [1.18, 2.0]; P=.002). No sex difference was observed in the prevalence of diabetes (RR=0.92; 95% CI [0.70, 1.22]); P=.57) and dyslipidemia (RR=1.33; 95% CI [0.88, 2.0]; P=.17). Cushing's disease has a worse clinical presentation in males and more diagnostic difficulties compared to females.

Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer

BackgroundMultiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. ObjectiveTo demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. Design, setting, and participantsThis multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. InterventionIn the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. Outcome measurements and statistical analysissPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. ConclusionsPatient enrolment began in March 2022, with recruitment expected to take 36 mo. Patient summaryFor patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies.