Normal Brain MRI Research Articles

A Clinical-Electrographic Profile of Neonatal Seizures and Their Etiologies in a Single Level III Neonatal Intensive Care Unit

Background: Seizures are the most frequent neurological emergency in neonatal period and can be associated with significant mortality and subsequent neuro-developmental disability if not recognized and managed early. Repaid identification of neonatal seizures and evaluation is critically required to identify and treat the underlying etiology. Clinicians face a major challenge in diagnosing and treating neonatal seizure because of inconspicuous clinical presentation, variable electro-clinical correlation. Assessing the combination of clinical presentation, etiological factors, different diagnostic tools, and treatments, can broaden the knowledge and understanding towards neonatal seizure providing better management and outcome. Objective: To study the characteristics of clinical and electrographic profile of neonatal seizure and the relations to their etiologies in neonatal intensive care unit. Methods: This is a descriptive cross sectional retrospective study of electronic health records with ICD- 10 diagnosis of neonatal seizure from birth to 28 days, who were admitted to neonatal intensive care unit at Sheikh Shakhbout Medical City between January 2020 to December 2021. Clinical data obtained including basic demographics: gender, gestational age, mode of delivery, birth weight, and Apgar score. Onset and type seizure, type of antiepileptic drugs administered, EEG findings, brain imaging, results of relevant laboratory tests and etiology of seizure were collected. Results: Total 31 neonates included in the study. Majority were male (71%), term (87%), and birth weight >2,5 kg (90%). Seizure within 24 hours was 58% and semiology was focal clonic in 32% of patient. No events in EEG in 81% and 6% had electrographic seizure (n=2). 94 % were treated with anti-convulsant, 86% of them before EEG. The majority (86%) received phenobarbitone as 1st line treatment and 83% received monotherapy. Leading causes of seizure were HIE (48%) followed by Vascular causes (16%). Seizure within 24 hours caused mainly by HIE (61%) and 60% of neonates with vascular and all infectious and genetic causes had seizure after 24 hours. In vascular causes, (60%) presented with focal clonic seizure. 60% of Multifocal epileptiform activity seen in HIE whereas focal presented more in vascular patient (36%). In HIE cases, 53% had normal brain MRI and 47% were abnormal. All cases with vascular causes had diagnostic abnormal MRI. The majority of HIE cases (87%) and all vascular cases received monotherapy. Conclusion: In this descriptive study of neonatal seizure, certain demographic data, clinical and electrographic characteristics had established links to their etiologies. Clinical events captured during EEG with no electrographic seizure are classified as non-epileptic clinical phenomenon. Diagnostic utility of EEG is required in diagnosis of involuntary movements and avoid unnecessary anti-seizure medications. Understanding the clinical-electrographic profile of neonatal seizure helps in the early recognition of specific etiologies, allowing an early diagnosis by organized diagnostic approach and management.

7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review

Abstract Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None. Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being Presentation: 6/1/2024

The significance of multimodality approach in the management of non-lesional drug-resistant focal parietal lobe epilepsies.

Due to extensive connectivity of the parietal lobe, non-lesional drug-resistant (DRE) parietal lobe epilepsies (PLEs) are difficult to localize and often imitate other epilepsies. Therefore, patients with PLEs have low rates of seizure freedom following epilepsy surgery. Previous studies have highlighted the need to combine EEG and semiology for more accurate localization of PLEs. As sophisticated tools for localization become more available, the use of multiple different neuroimaging and neurophysiologic diagnostic tests may more readily identify PLE. We hereby report a unique case of a complex localization in a non-lesional PLE, which was initially falsely localized to frontal lobe. This case underscores the utility of voxel-based morphometry (VBM) in identifying an epileptogenic lesion on a non-lesional MRI and the significance of multimodality approach including PET, magnetoencephalopathy (MEG), interictal and ictal EEG, semiology and cortical stimulation for accurate localization of PLEs. Understanding epilepsy through multimodality approach in this fashion can help with accurate localization especially in difficulty to localize and deceptive non-lesional PLEs. PLAIN LANGUAGE SUMMARY: Parietal lobe epilepsies are hard to pinpoint in the brain and can mimic other types of epilepsy, especially when brain MRIs appear normal. As sophisticated tools for locating epilepsies in the brain become more available, using multiple diagnostic tests may help identify parietal lobe epilepsies more easily. We describe a unique case of a parietal lobe epilepsy patient with normal brain MRI whose epilepsy was initially misidentified as being in the frontal lobe. Using various advanced diagnostic tests, we accurately found the epilepsy's true location in the parietal lobe and successfully treated the patient with surgery.

Diagnosis and Treatment of Spontaneous Intracranial Hypotension: Role of Epidural Blood Patching.

This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

Clinical analysis and literature review of two paediatric cases of anti-IgLON5 antibody-related encephalitis.

Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLA-DRB*10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms.

P030 Multiple autoantibody formation post COVID-19 infection

Abstract Background/Aims COVID-19 has been linked to the formation of a number of autoantibodies. This case is an important reminder to clinicians interpreting autoantibody results in conjunction with clinical manifestations. A previously fit 51 year old gentleman, with no prior history of autoimmune disease required admission with respiratory symptoms in April 2020 consistent with COVID-19 infection. His acute respiratory illness was complicated by empyema and left-sided pneumothorax requiring left pleural decortication and adhesiolysis under (VATS). Persistent respiratory symptoms and fatigue lead to investigations for long COVID. Positive antibodies detected were dsDNA 166IU/ml, Proteinase 3 antibodies 20IU/ml, Myeloperoxidase antibodies 32IU/ml, IgG anticardiolipin antibodies 90IU/ml and Glomerular basement membrane antibodies 351 IU/ml. Negative autoantibodies included ANA, RF, aCCP, b2GPI, smooth muscle, AMA and myositis related antibodies. Methods There were no clinical signs or symptoms of inflammatory arthropathy, vasculitis, thrombosis or connective tissue disease. Other investigations included a CT thorax showing no new lung lesions, unremarkable urine dipstick, normal urine ACR, normal US abdomen, CT sinuses and MRI brain. Results Trial course of prednisolone was given therapeutically due to long COVID symptoms. There was no significant impact on symptoms/ autoantibody titres thus steroids were discontinued. The patient was followed closely by the rheumatology team for two years. During that time, the autoantibody levels gradually decreased, and he did not develop clinical signs of autoimmune disease. His long COVID symptoms persisted, and he remains under the long COVID clinical team. Conclusion COVID-19 infection is known to cause an immune response. There have been published cases of positive ANA, U1-snRNP anti-SS-B/La, ANCA, anti-phospholipid and anti-SRP antibody formation following COVID-19 infection. The link between the pathophysiology of COVID-19, autoantibody formation and the role of autoimmunity is still unclear. This man's case was unusual in the number and variety of autoantibodies formed post COVID, this has not been reported in the literature to date. Some of the autoantibodies detected are highly specific for certain conditions, for example anti-GBM antibodies have a high specificity for Goodpasture’s syndrome, thus this case also illustrates the need to interpret positive autoantibodies in the context of clinical findings and history. Disclosure S. Islam: None. N. Erb: None.

Brain 18 F-FDG PET reveals cortico-subcortical hypermetabolic dysfunction in juvenile neuropsychiatric systemic lupus erythematosus

BackgroundIn juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE.MethodsA total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE).ResultsPatients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2–3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0–1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity.Conclusionsj-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI.

Volumetric analysis of age- and sex-related changes in the corpus striatum and thalamus in the 1-18 age group: a retrospective magnetic resonance imaging study.

Studies of the development and asymmetry of the corpus striatum and thalamus in early childhood are rare. Studies investigating these structures across the lifespan have not presented their changes during childhood and adolescence in detail. For these reasons, this study investigated the effect of age and sex factors on the development and asymmetry of the corpus striatum and thalamus in the 1-18 age group. In this retrospective study, we included 652 individuals [362 (56%) males] aged 1-18years with normal brain MRI between 2012 and 2021. Absolute and relative volumes of the corpus striatum and thalamus were obtained by segmentation of three-dimensional T1-weighted MRIs with volBrain1.0. We created age-specific volume data and month-based development models with the help of SPSS (ver.28). The corpus striatum and thalamus had cubic absolute volumetric developmental models. The relative volume of the caudate and thalamus (only males) is consistent with the decreasing "growth" model, the others with the decreasing cubic model. The absolute volumes of the males' bilateral corpus striatum and thalamus and the relative volumes of the caudate and thalamus of the females were significantly larger (P < 0.05). The caudate showed right > left lateralization; putamen, globus pallidus, and thalamus showed left > right lateralization.

A Cross-Sectional Study to Evaluate Diffusion Tensor Imaging Findings of the Brain in End-Stage Renal Disease (ESRD) Patients Undergoing Maintenance Hemodialysis Using Volume of Interest Method

Background: Cerebral small vessel disease (CSVD) is a chronic disorder affecting small vessels within the brain, increasing the risk of stroke in patients with chronic kidney disease (CKD). Diffusion tensor imaging (DTI) is a newer quantitative method for diagnosing CSVD at an early stage of pathogenesis. Objectives: This study compares various DTI parameters in multiple white matter tracts of the brain in CKD patients undergoing maintenance hemodialysis with normal controls in the Indian population using the volume of interest (VOI) method. Additionally, it correlates these DTI parameters with each other at different locations to gain insights into the pathogenesis of CSVD. Methods: After obtaining institutional ethics approval, a cross-sectional study was conducted at a tertiary care hospital over one year (June 2022 to May 2023). The study comprised seventy-five patients in the hemodialysis group and twenty-five controls. All participants underwent MRI brain examinations on a 3 Tesla MRI scanner, and the four DTI parameters - fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) - were reviewed for nine white matter tracts to evaluate statistical differences and correlations. Results: Fractional anisotropy was significantly decreased at anterior locations – corpus callosum genu (P = 0. 357 × 10-7), right anterior corona radiata (P = 0.001), and left anterior corona radiata (P = 0.45 × 10-5). In these locations, FA negatively correlated with RD (R = -0.7904, P &lt; 0.00001), and RD was also significantly increased. Axial diffusivity was significantly increased at posterior locations in the corpus callosum splenium (P = 0.108 × 10-5) and left posterior corona radiata (P = 0.244 × 10-5). However, none of the four DTI parameters showed significant differences between hemodialysis patients and the control group for the subset of patients with normal routine brain MRI features. The intraclass correlation coefficients (ICCs) were high for all four DTI parameters for both patients (0.78 to 0.85) and controls (0.82 to 0.89). Conclusions: This study on CKD patients undergoing maintenance hemodialysis reveals significant differences in some DTI parameters in widespread white matter tracts of the brain using the VOI method, with acceptable to excellent interobserver agreement.

Computer-Aided Diagnosis System for Automated Detection of Mri Brain Tumors

Detection and classification of brain tumors in manual or traditional way is an area which could be improved by having such automated detection and clarification system for brain tumors. In this paper, enhanced Computer-Aided Diagnosis CAD software system is introduced for brain tumor detection and classification. Total of 229 brain MRI images was taken as dataset for the purpose of this research; those dataset images include 105 normal brain MRI images, and 124 abnormal brain MRI images. Proposed CAD system is specialized for Meningioma brain tumor detection and classification, and the technique could be generalized and implemented for Glioma, and Pituitary brain tumors as well, and the whole system was implemented using MATLAB software. We started by cropping the region of interest (ROI) of dataset images. Then, feature extraction was implemented using first order statistical features, as well as using of some wavelets filters in combination with the former. T-test is used to exclude features of no statistical significance (p-value &lt; 0.05). After that, different types of classifiers were used to separate the normal set from the abnormal one. Note that, we used an iterative approach to by changing features with many runs until we got best performance, where, best accuracy results were gotten with SVM-Kernel Function (Linear), KNN-1, KNN-3, and KNN-5 classifiers. Note also that, we used convolutional neural networks (CNN) from Deep Learning toolbox of MATLAB as a control method to compare, where the images were fed directly to the CNN. The results were evaluated using performance assessment techniques which are Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Accuracy, Error Rate, and Area Under the Curve (AUC) of Reciever Operator Characteristic (ROC). With SVM classifier, the best gotten accuracy results were 91 % with CNN classifier, 82% with SVM classifier, and 77 % with KNN classifier. Furthermore, it was very beneficial to find such feature extraction techniques which gave acceptable accuracy results with three different classifiers; this was the case two times as mentioned the study. All proposed CAD system areas was developed and implemented using MATLAB software.

Searching The New Culprit of Optic Neuritis: The Role of Vitamin D

Abstract&#x0D; Introduction : Low vitamin D status has long been associated in multiple sclerosis patient with higher risk of disease progression and frequent relapses. Vitamin D plays an important role in modulating the immune process responsible for demyelination. To this date, the study on vitamin D deficiency in optic neuritis case is still rare.&#x0D; Case Illustration : Female, 20 years old, presenting with bilateral sudden visual loss since 1 week prior. The patient looked relatively pale and complained of accompanying headache and myalgia. Visual acuity in both eyes were light perception with dilated pupils and posterior segment showing optic disc swelling. CBC, infection and autoimmune screening came within normal limit and brain MRI further confirmed the presence of optic neuritis. The patient was given high dose intravenous steroid but showed no improvement. Later, she was screened for nutrient deficiency and found sign of low serum 25-hydroxyvitamin D. After one week of oral supplementation and neuroprotective agents, her vision drastically improved to 6/6 in both eyes.&#x0D; Discussion : Vitamin D deficiency nowadays is getting more prevalent in high risk individuals with low dietary intake and sunlight exposure. Recent study found that mean serum vitamin D level were significantly lower in autoimmune optic neuritis (ON) and were associated with ON attack severity. Vitamin D sufficiency is associated with better inflammatory outcome and long term neurodegenerative measures in demyelinating diseases, as shown by improvement in RNFL thickness after attack.&#x0D; Conclusion : Screening for vitamin D deficiency is essential to consider in managing patient with atypical optic neuritis.

"Clock dial pattern", a radiologic clue to neuro-chikungunya diagnosis: a case series.

Chikungunya is a mosquito-borne disease caused by the chikungunya virus (CHIKV) and can lead to neurological complications in severe cases. This study examined neuroimaging patterns in chikungunya cases during two outbreaks in Brazil to identify specific patterns for diagnosis and treatment of neuro-chikungunya. Eight patients with confirmed chikungunya and neurological involvement were included. Clinical examinations and MRI scans were performed, and findings were analyzed by neuroradiologists. Data on age, sex, neurological symptoms, diagnostic tests, MRI findings, and clinical outcomes were recorded. Patients showed different neuroimaging patterns. Six patients exhibited a "clock dial pattern" with hyperintense dotted lesions in the spinal cord periphery. One patient had thickening and enhancement of anterior nerve roots. Brain MRI revealed multiple hyperintense lesions in the white matter, particularly in the medulla oblongata, in six patients. One patient had a normal brain MRI. The "clock dial pattern" observed in spinal cord MRI may be indicative of chikungunya-related nervous system lesions. Isolated involvement of spinal cord white matter in chikungunya can help differentiate it from other viral infections. Additionally, distinct brainstem involvement in chikungunya-associated encephalitis, particularly in the rostral region, sets it apart from other arboviral infections. Recognizing these neuroimaging patterns can contribute to early diagnosis and appropriate management of neuro-chikungunya.

Alzheimer Disease Pathology and Neurodegeneration in Midlife Obesity: A Pilot Study.

Obesity and excess adiposity at midlife are risk factors for Alzheimer disease (AD). Visceral fat is known to be associated with insulin resistance and a pro-inflammatory state, the two mechanisms involved in AD pathology. We assessed the association of obesity, MRI-determined abdominal adipose tissue volumes, and insulin resistance with PET-determined amyloid and tau uptake in default mode network areas, and MRI-determined brain volume and cortical thickness in AD cortical signature in the cognitively normal midlife population. Thirty-two middle-aged (age: 51.27±6.12 years, 15 males, body mass index (BMI): 32.28±6.39 kg/m2) cognitively normal participants, underwent bloodwork, brain and abdominal MRI, and amyloid and tau PET scan. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi-automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer was used to automatically segment brain regions using a probabilistic atlas. PET scans were acquired using [11C]PiB and AV-1451 tracers and were analyzed using PET unified pipeline. The association of brain volumes, cortical thicknesses, and PiB and AV-1451 standardized uptake value ratios (SUVRs) with BMI, VAT/SAT ratio, and insulin resistance were assessed using Spearman's partial correlation. VAT/SAT ratio was associated significantly with PiB SUVRs in the right precuneus cortex (p=0.034) overall, controlling for sex. This association was significant only in males (p=0.044), not females (p=0.166). Higher VAT/SAT ratio and PiB SUVRs in the right precuneus cortex were associated with lower cortical thickness in AD-signature areas predominantly including bilateral temporal cortices, parahippocampal, medial orbitofrontal, and cingulate cortices, with age and sex as covariates. Also, higher BMI and insulin resistance were associated with lower cortical thickness in bilateral temporal poles. In midlife cognitively normal adults, we demonstrated higher amyloid pathology in the right precuneus cortex in individuals with a higher VAT/SAT ratio, a marker of visceral obesity, along with a lower cortical thickness in AD-signature areas associated with higher visceral obesity, insulin resistance, and amyloid pathology.

Kelch-like Protein 11 (KLHL11) Antibodies in Children With Seizures of Undetermined Cause.

Kelch-like protein 11 (KLHL11)-antibody may be found in paraneoplastic neurological disorders presenting with epileptic seizures. The aim of this study was to investigate the prevalence and clinical significance of KLHL11-antibody in epilepsy. Sera of 42 pediatric and 59 adult patients with seizures of undetermined cause were screened using a cell-based assay. KLHL11-antibody was found in three of 168 control patients with paraneoplastic neurological disorders and four pediatric patients (4-8-year-old, 2 boys/2 girls) with seizures of unknown cause presenting with myoclonic-atonic epilepsy, generalized epilepsy or childhood epilepsy with centrotemporal spikes. In these four cases, seizures continued for 2-7 months, responded promptly and favorably to conventional anti-seizure drugs and did not recur in follow-up durations ranging between 2-5 years. Patients had normal brain MRI findings and motor-mental development before and after seizures. KLHL11-antibody was not detected in adult epilepsy patients with undetermined cause, MOG antibody-positive patients and healthy controls. KLHL11-antibody may be detected in pediatric epilepsy patients with a relatively benign disease course.

Visceral Abdominal Adipose Tissue and Insulin Resistance Respectively Influence Alzheimer Disease Amyloid Pathology and Neurodegeneration in Midlife

AbstractBackgroundObesity and adiposity at midlife, evidenced by high body mass index (BMI), are increasingly understood as a risk factor for Alzheimer’s disease (AD). Importantly, visceral fat is known to be associated with insulin resistance and proinflammatory state, the mechanisms involved in AD pathology. Herein, we aimed to assess the association between brain MRI volumes as well as amyloid and tau uptake with obesity, insulin resistance, and abdominal adipose tissue in cognitively normal midlife population.MethodA total of 34 middle‐aged (age: 51.27 ± 6.12 years, BMI: 32.28 ± 6.39 kg/m2), cognitively normal participants, underwent bloodwork, brain and abdominal MRI, as well as amyloid and tau PET scan. Homeostatic Model Assessment for Insulin Resistance (HOMAIR) &gt; 1.9 was used as a measure of insulin resistance. Visceral and subcutaneous adipose tissue (VAT, SAT) were semi‐automatically segmented using VOXel Analysis Suite (Voxa). FreeSurfer 7.1.1 was used for automatic segmentation of cortical and subcortical brain regions using a probabilistic atlas. Dynamic amyloid imaging was performed with a bolus injection of ∼15 mCi of [11C]PiB, followed by a 60‐min scan. A single intravenous bolus of between 7.2‐10.8 mCi of AV‐1451 was administered. Data from the 30‐60 minute, and 80‐100 minute post‐injection window for PiB and AV‐1451 were used for the analysis, respectively. The association of brain volumes and PiB and AV‐1451 SUVRs within the default mode network areas with BMI and VAT/SAT ratio were assessed using linear regression models.ResultWe observed lower right entorhinal white matter volumes in obese participants with insulin resistance compared to metabolically normal non‐obese group (p = 0.004), without any significant difference in PiB or AV‐1451 SUVRs. Regression models with sex, age and education as covariates showed a significant positive association between VAT/SAT ratio and left precuneus white matter PiB SUVRs (R2 = 0.31, p = 0.005), but no significant associations with AV‐1451 SUVRs.ConclusionIn our midlife obese sample with insulin resistance, there were lower right entorhinal white matter volume, which is involved in relaying information to the hippocampus. We also demonstrate higher early amyloid pathology in AD‐signature areas such as the precuneus in mid‐life persons with high VAT/SAT ratio, a marker of visceral obesity.

Body Mass Index, but not Visceral Abdominal Obesity and Insulin Resistance, Negatively Impacts White Matter Microstructure in Midlife

AbstractBackgroundMidlife obesity, as evidenced by high body mass index (BMI), is increasingly understood as a risk factor for development of Alzheimer’s disease. Importantly, visceral fat, by producing adipokines, contributes to inflammation as well as insulin resistance, mechanisms involved in development of Alzheimer’s disease. Herein, we aimed to assess association of white matter microstructure, measured by Diffusion tensor imaging (DTI), with obesity and abdominal adipose tissue composition at midlife.MethodA total of 34 middle‐aged (age: 51.27 ± 6.12 years, BMI: 32.28 ± 6.39 kg/m2), cognitively normal participants, underwent bloodwork, brain and abdominal MRI. Insulin resistance status was assessed using Homeostatic Model Assessment for Insulin Resistance. Abdominal visceral and subcutaneous adipose tissue (VAT, SAT) were automatically segmented using VOXel Analysis Suite (Voxa) and VAT/SAT ratio was calculated. A diffusion spectrum imaging scheme with a total of 98 diffusion samplings and a voxel size of 2 mm was acquired. Using DSI studio (https://dsi‐studio.labsolver.org/), the diffusion data were reconstructed using generalized q‐sampling imaging and the tensor metrics were calculated. Fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD, respectively) for white matter tracts were compared across study groups using one‐way ANOVA. Multiple regression models with sex, age, and education as covariates were used to assess the association of BMI, VAT/SAT ratio, and HOMA‐IR with DTI metrics.ResultOur data showed that BMI was negatively associated with AD values in right inferior fronto‐occipital fasciculus, tapetum and forceps major of Corpus Callosum (CC), superior and middle cerebellar peduncle, and bilateral reticular tract. The negative association of BMI with AD values in tapetum of CC was significant only in women. Right reticular tract MD and superior cerebellar peduncle MD and RD values were also significantly associated with BMI. There were no significant associations between neither of diffusion metrics and VAT/SAT ratio or HOMA‐IR.ConclusionAssociation of midlife obesity with lower axonal diffusivity, reflective of lower white matter integrity, with differential patterns in men and women especially in CC, is in line with previous findings in healthy individuals. Reduced axonal diffusivity in reticular and brain stem pathways could be indicative of early dysregulations observed in Alzheimer’s disease.

THU172 Accuracy Of The Glucagon Testing In The Diagnosis Of Growth Hormone Deficiency During Transition

Abstract Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1&amp;lt;0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 &amp;lt;-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value &amp;lt;6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s &amp;lt;0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s &amp;lt;0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P&amp;lt;0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P&amp;lt;0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P&amp;lt;0.001) and omGHD (0.6; IQR 0.1- 1.8, P&amp;lt;0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value &amp;lt;6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values &amp;lt;0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

18F]DPA-714 PET Imaging in the Presurgical Evaluation of Patients With Drug-Resistant Focal Epilepsy.

Translocator protein 18 kDa (TSPO) PET imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [18F]DPA-714 PET and [18F]FDG PET for localizing the EZ during presurgical assessment of DRFE, when phase 1 presurgical assessment does not provide enough information. We compared [18F]FDG and [18F]DPA-714 PET images of 23 patients who had undergone a phase 1 presurgical assessment, using qualitative visual analysis and quantitative analysis, at both the voxel and the regional levels. PET abnormalities (increase in binding for [18F]DPA-714 vs decrease in binding for [18F]FDG) were compared with clinical hypotheses concerning the localization of the EZ based on phase 1 presurgical assessment. The additional value of [18F]DPA-714 PET imaging to [18F]FDG for refining the localization of the EZ was assessed. To strengthen the visual analysis, [18F]DPA-714 PET imaging was also reviewed by 2 experienced clinicians blind to the EZ location. The study included 23 patients. Visual analysis of [18F]DPA-714 PET was significantly more accurate than [18F]FDG PET to both, show anomalies (95.7% vs 56.5%, p = 0.022), and provide additional information to refine the EZ localization (65.2% vs 17.4%, p = 0.019). All 10 patients with normal [18F]FDG PET had anomalies when using [18F]DPA-714 PET. The additional value of [18F]DPA-714 PET seemed to be greater in patients with normal brain MRI or with neocortical EZ (especially if insula is involved). Regional analysis of [18F]DPA-714 and [18F]FDG PET provided similar results. However, using voxel-wise analysis, [18F]DPA-714 was more effective than [18F]FDG for unveiling clusters whose localization was more often consistent with the EZ hypothesis (87.0% vs 39.1%, p = 0.019). Nonrelevant bindings were seen in 14 of 23 patients in visual analysis and 9 patients of 23 patients in voxel-wise analysis. [18F]DPA-714 PET imaging provides valuable information for presurgical assessments of patients with DRFE. TSPO PET could become an additional tool to help to the localization of the EZ, especially in patients with negative [18F]FDG PET. Eudract 2017-003381-27. Inclusion of the first patient: September 24, 2018. This study provides Class IV evidence on the utility of [18F]DPA-714 PET compared with [18F]FDG PET in identifying the epileptic zone in patients undergoing phase 1 presurgical evaluation for intractable epilepsy.

351 Snapshot of Transient Ischaemic Attack inpatient management at a model three Irish hospital

Abstract Background Transient Ischaemic Attack (TIA) is a common presentation to hospitals and portends a high risk for eventual stroke. The EXPRESS study suggested the benefit of urgent outpatient assessment of TIA, which was associated with a 80% risk reduction of early recurrent stroke when compared to usual care. The HSE model of care for stroke endorses that rapid access TIA clinics could reduce costs of hospital admissions. Average length of admission for TIA is 6.7 days in Ireland. This study aimed to examine TIA admission lengths and identify possible targets for improvement in a model three Irish hospital. Methods All patients with a HIPE coded diagnosis of ‘Transient Ischaemic Attack’ from 17/12/21 to 20/8/22 were included. All coded diagnoses of ‘Transient Ischaemic Attack’ had a normal MRI brain DWI—abnormal MRI DWI imaging is coded as stroke. Therefore the true number of TIAs was not captured. Hospital electronic databases were used to identify baseline demographics, date of inpatient investigation request and date of inpatient investigation completion. Results 64 cases were identified. The median age was 79 years (interquartile range 67 to 86 years). 45% were female. 52% were admitted under a stroke/geriatric team. Median length of admission was 4 days (IQR 3 to 7 days). CT was requested on median day 0. MRI, carotid doppler US and echocardiogram were requested on a median day 1. 94% underwent CT brain imaging on median day 1. 34 (53%) underwent MRI brain DWI, on median day 3. 13 (20%) underwent carotid doppler US, on median day 3. 20 (31%) underwent echocardiogram, on median day 4. Conclusion Length of hospital stay has improved compared to prior studies. Limited access to investigations may prolong hospital stay. Streamlining services with development of urgent outpatient TIA clinics, could improve outcomes, save clinician time, free up hospital beds and save hospital funding.

Structural brain network analysis in occipital lobe epilepsy

BackgroundThis study aimed to analyze the structural brain network in patients with occipital lobe epilepsy (OLE) and investigate the differences in structural brain networks between patients with OLE and healthy controls.MethodsPatients with OLE and healthy controls with normal brain MRI findings were enrolled. They underwent diffusion tensor imaging using a 3.0T MRI scanner, and we computed the network measures of global and local structural networks in patients with OLE and healthy controls using the DSI studio program. We compared network measures between the groups.ResultsWe enrolled 23 patients with OLE and 42 healthy controls. There were significant differences in the global structural network between patients with OLE and healthy controls. The assortativity coefficient (-0.0864 vs. -0.0814, p = 0.0214), mean clustering coefficient (0.0061 vs. 0.0064, p = 0.0203), global efficiency (0.0315 vs. 0.0353, p = 0.0086), and small-worldness index (0.0001 vs. 0.0001, p = 0.0175) were lower, whereas the characteristic path length (59.2724 vs. 53.4684, p = 0.0120) was higher in patients with OLE than those in the healthy controls. There were several nodes beyond the occipital lobe that showed significant differences in the local structural network between the groups. In addition, the assortativity coefficient was negatively correlated with the duration of epilepsy (r=-0.676, p = 0.001).