All Articles

Abdullah Emre Taçyıldız¹*, Melih Üçer²

¹Department of Neurosurgery, Karabük University Faculty of Medicine, Karabük, Turkey

²Department of Neurosurgery, Biruni University Faculty of Medicine, Istanbul, Turkey

Objective: This study aims to analyze the limitations of human visual perception, compare them with the visual adaptations of other species, and explore how technological advancements—such as artificial intelligence, medical imaging, and augmented reality—have improved medical diagnostics and surgical precision.

Methods: A structured literature review was conducted, incorporating comparative analyses of visual perception across species, including frogs, dragonflies, and humans. The study evaluated the role of advanced imaging technologies, artificial intelligence-based diagnostics, and digital image processing tools in overcoming the limitations of biological vision. Selection criteria for species comparisons were based on functional adaptations and their relevance to medical imaging applications.

Results: Findings indicate that species-specific visual adaptations are optimized for survival rather than accuracy. Human vision, while advanced, is inherently constrained by physiological and neurological limitations. However, medical imaging technologies, including fluorescence-guided surgery, histology, and AI-assisted diagnostics, have significantly enhanced the precision of visual interpretation in clinical settings. The integration of computational tools, such as Adobe Photoshop for forensic and radiological analysis, further refines image accuracy and medical decision-making.

Conclusion: The interplay between biological vision and technological advancements underscores the necessity of integrating artificial intelligence and advanced imaging in medical practice. Future research should focus on optimizing these technologies to further enhance diagnostic accuracy, surgical precision, and clinical outcomes, ultimately pushing the boundaries of human visual perception.

Ilya Adamchic

Department of Radiology, Vivantes Hospital im Friedrichshain, Berlin, Germany

Intracranial aneurysms (IAs) pose a significant public health challenge due to their potential for rupture and associated morbidity and mortality. Despite advancements in imaging technologies such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA), detecting small, incidental IAs remains challenging, particularly amid increasing global imaging volumes and resource constraints. Artificial intelligence (AI) has emerged as a transformative tool in medical imaging, demonstrating potential to enhance diagnostic accuracy and efficiency. Deep learning models, particularly convolutional neural networks (CNNs), have shown near-expert accuracy in detecting subtle aneurysmal features, enabling early diagnosis and improving clinical workflows. AI-driven approaches extend beyond detection to include rupture risk assessment, predictive diagnostics, and treatment planning, thereby improving patient-specific care and reducing unnecessary interventions.

However, challenges such as false-positive rates, ethical considerations, and the need for robust validation studies hinder AI adoption in clinical practice. This review contextualizes recent advancements and the findings of Adamchic et al. (2024), within the broader landscape of AI applications in IA diagnostics. It discusses AI’s role in addressing diagnostic variability, mitigating radiologist workloads, and enhancing reproducibility, particularly for junior clinicians. The article also explores barriers to widespread implementation, including data safety, algorithm transparency, and financial constraints, while emphasizing the need for collaborative efforts to refine AI models and integrate them seamlessly into radiology workflows. By addressing these challenges, AI has the potential to revolutionize intracranial aneurysm management, improving patient outcomes and transforming modern radiology practices.

Huma Ikram

Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan

Nanomedicine is going to be a novel and different avenue of therapy for the neurological patients, overcoming blood-brain barrier difficulties while also addressing the unique complexity of neurological diseases. With applications of nanoparticles, including liposomes, dendrimers, exosomes, and polymeric nanoparticles, effective drug delivery will be possible via targeted and controlled release and reduced adverse effects. These technological breakthroughs are going to be of great help in the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's, and in conditions like multiple sclerosis. Because of this, nanomedicine has a great promise in the field of neuroinflammatory conditions as well. In addition, nanomedicine is going to play a significant role in precision medicine, where therapies can be planned according to the genetic, molecular, and biological makeup of the patients. However, precision in diagnosis and monitoring will also provide a personalized treatment regimen as nanotechnology can be integrated with other advanced diagnostic technologies like MRI, PET, and biomarker detection. Although it has a lot of promise, clinical translation has not avoided the same problems that have proved to be highly disconcerting for so many developments in nanomedicine, including issues of biocompatibility, safety, and, in the case of some products, regulatory approval. Addressing these factors will prove critical for the successful embedding of nanomedicine into the routine neurological care system. This review touches on the current status of nanomedicine in neurology, the promise that it holds for precision treatments, and the barriers that apply to its ability to effect real clinical practice portrayals, thereby providing an insight into the future of personalized therapy in neurology.

Vivian S. Nguyen^1*, Griffin J. Young², Adil Javed¹, Timothy J. Carroll²

¹Department of Neurology, The University of Chicago, Chicago, IL, USA

²Department of Radiology, The University of Chicago, Chicago, IL, USA

MRI has long been a critical tool for diagnosing and monitoring Multiple Sclerosis (MS). Conventional MRI employed in clinical practice is non-parametric, which disallows quantitative measures of tissue damage. This creates an unmet need to develop a post-acquisition image processing algorithm that can convert a qualitative image into a corresponding quantitative map. We present a methodology that can convert a clinically routine T1-weighted MPRAGE image into a parametric T1 map with high accuracy and precision in relation to a commonly used T1 mapping reference standard. We evaluate the methodology’s performance in Multiple Sclerosis for the purpose of quantifying tissue damage primarily in lesions and secondarily in white matter and gray matter regions.

Liping Wu, Tao Lv^*

The People’s Hospital of Deyang, North Taishan Road, Deyang, Sichuan, China

As of now, there are increasing cases related to oculogyric crisis (OGC), mainly focusing on clinical manifestations. The pathogenesis of OGC is still uncertain, and there is no unified treatment protocol. This review aims to explore the treatment and management strategies for OGC based on existing cases, hoping to provide references for clinicians in identifying and treating OGC in practice.

Andressa Gonçalves Rodrigues-Fândhrs¹, Bruna Kulmann-Leal¹, José Artur Bogo Chies^2*

¹Postgraduate Program in Genetics and Molecular Biology (PPGBM), Universidade Federal do Rio Grande do Sul – UFRGS, Porto Alegre, Brazil

²Laboratory of Immunobiology and Immunogenetics, Department of Genetics, Federal University of Rio Grande do Sul – UFRGS, Porto Alegre, Brazil

Huitong Ding^1,2*, Sanskruti Madan¹, Rhoda Au^1,2,3,4,5,6, P. Murali Doraiswamy⁷, Chunyu Liu^2,8

¹Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

²The Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

³Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

⁴Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

⁵Slone Epidemiology Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

⁶Departments of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

⁷Neurocognitive Disorders Program, Departments of Psychiatry and Medicine, and the Duke Institute for Brain Sciences, Duke University School of Medicine, Durham, NC, USA

⁸Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

Accumulating evidence suggests that reproductive markers, such as age at menarche, are associated with cognitive function and the risk of developing Alzheimer's disease (AD). These reproductive markers offer promising potential for predicting the risk of AD, underscoring the necessity for sex-specific considerations in understanding and managing this neurodegenerative disorder. This review first discusses recent findings on reproductive markers in AD progression, and further points out the direction for future research to unravel the complex interplay between reproductive health and cognitive health. We advocate for the incorporation of sex heterogeneity into AD precision medicine to tailor sex-specific diagnostic and intervention approaches.

Hirotaka Nomiya¹, Masami Yamada^1,2*

¹Department of Cell Biology and Biochemistry, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Matsuoka Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, Japan

²Life Science Innovation Center, University of Fukui, Bunkyo, Fukui-City, Fukui, Japan

The interactions between genetic and environmental factors (G x E interactions) play a crucial role in the pathogenesis of schizophrenia. The administration of phencyclidine, a psychotropic drug, to Kpna1-deficient mice induces behavioral abnormalities resembling schizophrenia. In the nucleus accumbens of these mice, the expressions of dopamine receptors, an RNA editing enzyme, and cytoplasmic dynein demonstrate gene-environment interaction-dependent alterations. Kpna1-deficient mice may be useful as a gene-environment interaction model for schizophrenia and provide insights into its pathogenesis. Further, changes in gene expression in the nucleus accumbens may be involved in the development of schizophrenia.

Dr. Robert W Baumhefner

Neurology Service, Veterans Administration West, Los Angeles Healthcare Center, Los Angeles, CA, USA;

Sarah Kawtharani¹, Elias Horanieh², Bader Ali³, Mohammad Housheimy¹, Houssein Darwish^1*

¹Department of Neurosurgery, American University of Beirut Medical Center, Beirut, Lebanon

²Department of Surgery, University of Balamand, Beirut, Lebanon

³Medical Student, University of Balamand, Beirut, Lebanon

Background: Contrast Induced Encephalopathy is a known but rare complication of endovascular procedures. Patients show neurologic symptoms mimicking a stroke and include visual disturbances, motor or sensory deficits, headache, seizures, memory loss, confusion, aphasia, and coma. Irreversible neurological symptoms are rare and fatal encephalopathy is even more so.

Case Report: In this article we present a case of a 75-year-old female patient who showed neurological symptoms mimicking a stroke post cerebral Digital Subtraction Angiography that was done with Iohexol as a contrast agent, as a diagnostic work up to rule out a ruptured aneurysm. Further investigations showed no arterial spasms nor dissection. Symptoms reappeared after the second contrast administration but completely resolved after the administration of steroids and fluids.

Conclusion: Contrast Induced Encephalopathy should be further investigated with imaging to rule out other thromboembolic or hemorrhagic causes. Treatment via the administration of steroids and fluids have shown to be effective with complete remission of symptoms.

Fumiaki Iwane^1*, Brian Johnson², Leonardo G Cohen¹

¹Human Cortical Physiology and Neurorehabilitation Section, NINDS, NIH, Bethesda, MD, USA

²Department of Occupational Therapy, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA

Itzhak Kurek^*, Jean-Christophe Quillet, Michael Siani-Rose

Cannformatics, Inc., San Francisco, CA, USA

Autism spectrum disorder (ASD) is a group of lifelong heterogeneous neurodevelopmental conditions with a wide range of severity levels that affect social communication and social interaction. Diagnosis of ASD relies on subjective observation of these clinical phenotypes. The growing body of big data generated by subjective methods and more recently by objective high-throughput technologies such as omics for the detection of biomolecules, is being successfully applied to a rapidly-growing number of machine learning (ML) algorithms to inform research for diagnostics and interventions for patients with ASD. While most reviews in this area are focused on the ML approaches, we highlight the impact of the database on the expected outcomes in ML-based ASD research studies.

Martina von der Bey^1,2, Ebru Ercan-Herbst^1*

¹BioMed X Institute, Im Neuenheimer Feld, Heidelberg, Germany

²Molecular and Translational Neuroscience, Department of Neurology, Ulm University, Albert-Einstein-Allee, Ulm, Germany

One of the biggest challenges in the field of neurological disorders is the limited availability of freshly dissected human brain tissue. Therefore, the use of human induced pluripotent stem cells (hiPSCs) is important to develop human brain-like models to study the interaction of different brain cell types in health and disease. For physiologically relevant disease modeling, three-dimensional (3D) cell culture systems are of great importance because they provide a more representative in vivo-like micro-environment to the cells. The field of 3D cell culture systems using diverse hiPSC-derived cells is growing and gets steadily advanced. However, to this day, there is no cell culture model available that includes all brain cell types. Here, we review the latest improvements of 3D hiPSC-based cell culture systems in the field of neuroscience. We focus on innovations for the generation of neurons, astrocytes, oligodendrocytes, microglia as well as endothelial cells and pericytes.

Robert B. Slocum

Narrative Medicine Program Coordinator, University of Kentucky HealthCare, Lexington, Kentucky, USA

Neda Jafri¹, Savanna Dasgupta¹, James E. Siegler^1,2*

¹Cooper Neurological Institute, Cooper University Health Care, Camden, NJ, USA

²Cooper Medical School of Rowan University, Camden, NJ, USA

Endovascular thrombectomy (EVT) revolutionized the treatment for acute ischemic stroke due to large vessel occlusion (LVO). Current guidelines published by multiple academic societies recommend EVT for eligible patients who present within 24 hours of the time last seen well. However, more recent data suggests that extending this window past 24 hours produces more favorable outcomes in specific patients presenting with anterior circulation LVO. More specifically, recent observational data indicates a higher probability of functional independence, functional improvement, and long-term survival with EVT when compared to best medical management. Based on the available data, there is unclear equipoise in randomizing all patients with acute ischemic stroke due to LVO to EVT or medical management. However, for those patients with large established infarction, distal occlusions, or well beyond the 24-hour window, randomized clinical trials are called upon to determine whether there is benefit of EVT in these patient groups. In this narrative review, we will summarize the most recent data on EVT in the ultra extended window (>24 hours after time last seen normal) and discuss further considerations of this treatment.

Christopher Nardone^1,2, Xin Gu³, Stephen J. Elledge^1,2*

¹Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA, USA

²Department of Genetics, Harvard Medical School, Boston, MA, USA

³Department of Neurobiology, Harvard Medical School, Boston, MA, USA

The MiT/TFE proteins (MITF, TFE3, TFEB, and TFEC) constitute a family of transcription factors that maintain cellular homeostasis by controlling the transcription of genes involved in lysosomal biogenesis, autophagy, oxidative metabolism, and pigmentation. While significant effort has been placed in understanding the downstream function of this family, the upstream regulation has only recently become clearer. It was appreciated that the nutrient-sensing Rag GTPases-mTORC1 pathway attenuates the activity of this family, but how this occurs mechanistically remained unclear. The physiological role of the MiT/TFE family is underscored by the fact that numerous human diseases are caused by their misregulation. The goal of this minireview is to provide a summary of recent findings that have elucidated how this family is regulated upstream and, hence, the molecular basis of a rare kidney cancer and neurodevelopmental syndrome caused by mutations in TFE3. The information presented here may serve as a framework for future studies.

Sai Krishna Vallamchetla

All India Institute of Medical Sciences, Bhopal, India

The ketogenic diet (KD) has emerged as a promising therapeutic strategy for a variety of neurological disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. The potential benefits of the KD are attributed to its capacity to modulate neurotransmission, reduce inflammation, improve mitochondrial function, and enhance synaptic plasticity. Despite the growing body of evidence supporting the KD's therapeutic potential, there remain challenges in its implementation, such as potential side effects, nutrient deficiencies, and the need for careful monitoring by healthcare professionals. Factors affecting the success of the KD include patient adherence, individual metabolic response, and appropriate diet customization. This review summarizes the current evidence supporting the KD's role in the management of neurological disorders, discusses the underlying mechanisms of action, highlights the challenges and considerations associated with its use, and addresses the factors that can influence treatment success. Further research is needed to optimize the KD for different patient populations, elucidate the specific therapeutic mechanisms, and identify potential biomarkers to predict treatment response, ultimately enhancing the quality of life and overall well-being of individuals affected by neurological disorders.

Connor Farrell, Keeley J Brookes^*

Biosciences, Nottingham Trent University, Clifton Campus, Nottingham, NG8 11NS, UK

The APOE gene and particularly the ε4 allele have been a long-established risk factor for Alzheimer’s disease (AD), demonstrating the largest genetic effect size in this complex disease. In light of the odds ratios observed for the risk allele, many studies disregard neighbouring association signals as merely “tagging” this effect. Polygenic risk score (PRS) analyses in this field regularly use low linkage disequilibrium parameters (r²≥0.1) when selecting SNPs for analysis across the genome and remove kilobases of data surrounding the APOE locus, preventing confounding factors influencing their results. This study investigated a 500kb region surrounding the APOE locus, utilising PRS analysis to explore whether additional SNPs in this region could be providing contributory effects to AD predictability. The data presented here suggest that the “sphere of influence” of the APOE isoform SNPs covers a region of around 92kb; SNPs in Linkage Disequilibrium (LD) at r²<0.4 with rs429358 potentially contribute independently to the PRS predictability for AD, and that there are additional independent SNPs in this region that have increased effects in an APOE ε4 negative sample. This study concludes that further consideration is required when selecting LD parameters for PRS analysis and that additional investigation into the region surrounding APOE may yield polymorphisms that may play a pivotal role in the development of AD.

Effie-Photini C. Tsilibary^1,2, Danielle Carlson^1,2, Apostolos P. Georgopoulos^1,2*

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Gulf War Illness (GWI) afflicted many veterans of the 1990-91 Gulf War with multiple symptoms worsening with time. The reasons for GWI have not been elucidated but may include toxicity due to inflammatory factors induced by vaccines administered to deployed and nondeployed veterans. In particular, the anthrax vaccine may have harmful effects in veterans lacking specific protective HLA alleles, as we reported previously, using a murine neuroblastoma N2A cell culture system. Lack of these protective alleles could allow several vaccine antigens to circulate chronically, resulting in protracted low-grade inflammation accompanying the disease. When N2A cells were exposed to GWI serum or the antigen of the anthrax vaccine, the cells underwent apoptosis due to compromised cell membrane, mitochondrial and cytoskeletal function.  Elucidation of mechanisms of GWI should provide clues for therapy. Since antigen-induced inflammation accompanies GWI and stem cells were reported to have antimicrobial activity, we examined the effect of murine stem cells co-cultured with N2A cells before exposure to GWI serum and also Protective Antigen PA63, the main component of the anthrax vaccine. The presence of stem cells completely prevented GWI serum toxicity, since it resulted in inhibition of apoptosis. Moreover, cultures of stem cells exposed to PA63 resulted in the degradation of this antigen. We conclude that stem cells can protect against vaccine-induced toxic components of the GWI serum in N2A cells, prompting further studies on the possible beneficial effects of these cells in GWI.

Davis B. Rippee¹, Gabriella E. Glassman², Sara C. Chaker³, Patrick E. Assi⁴, Jennifer Black, Alonda C. Pollins⁴, Jun Yao⁴, Wesley P. Thayer^4,6*

¹University of Mississippi School of Medicine, Jackson, MS, USA

²Florida State University College of Medicine, Tallahassee, FL, USA

³Vanderbilt University, Nashville, TN, USA

⁴Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

⁵Meharry Medical College, Nashville, TN, USA

^6*Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

Introduction: Peripheral nerve injuries commonly result from trauma and can lead to devastating loss of sensory and motor function. A novel strategy to improve peripheral nerve regeneration is a chemical fusogen known as polyethylene glycol (PEG). Several animal studies have illustrated PEG’s potential to help prevent axon loss after peripheral nerve injury. However, the relative rate of success and potential complications of these studies have not been definitively shown in the literature. The purpose of this systematic review is to evaluate the literature regarding the success of PEG adjunct treatment after peripheral nerve injury in preclinical models.

Materials and Methods: The MEDLINE database was queried using the PubMed search engine with the following keywords and phrases: “polyethylene glycol” OR “PEG” AND “nerve” AND “fusion”. All resulting articles were screened by two reviewers. Animal type, nerve type, injury type, type(s) of analyses, and overall superiority of outcomes were assessed.

Results: One-hundred and seventy-nine articles were identified, and thirteen studies remained after the application of inclusion and exclusion criteria. Twelve of the thirteen studies utilized rats as the preclinical model, while one utilized a guinea pig. Superiority of peripheral nerve repair outcomes with adjunct PEG treatment compared to a control group was reported in eleven of thirteen studies.

Conclusions: The majority of studies reported positive outcomes when using PEG; this indicates that PEG treatment has the potential to enhance peripheral nerve regeneration after injury. However, the results of some of these studies indicated several uncertainties that need to be addressed in future studies. These preclinical models may help guide clinicians regarding the use of PEG treatment in peripheral nerve repair.

Lisa M. James^1,2,3,4, Brian E. Enghdal^1,2,4,5,, Arthur C. Leuthold^1,2, Apostolos P. Georgopoulos^1,2,3,4,6*

¹The PTSD Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

³Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

⁴Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA

⁵Department of Psychology, University of Minnesota, Minneapolis, MN, USA

⁶Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA

Previous research has demonstrated highly accurate classification of veterans with posttraumatic stress disorder (PTSD) and controls based on synchronous neural interactions (SNI), highlighting the utility of SNI as a biomarker of PTSD. Here we extend that research to classify additional trauma-related outcomes including subthreshold PTSD, partial recovery, and full recovery according to SNI. A total of 219 U.S. veterans completed diagnostic interviews and underwent a magnetoencephalography (MEG) scan from which SNI was computed. Linear discriminant analysis was used to classify the PTSD and control brains, achieving 100% accuracy. That discriminant function was then used to classify each brain in the subthreshold PTSD, partial recovery, and full recovery diagnostic groups as PTSD or Control. All of the subthreshold PTSD diagnostic group were classified as PTSD, as were three-quarters of the partial recovery group. Findings regarding the full recovery group were mixed, documenting variability in the functional brain status of PTSD recovery. The results of the present study add to the literature supporting the discriminatory power of MEG SNI and demonstrate the utility of SNI as a biomarker of various PTSD-related trajectories.

Shervin Assari^1,2*

¹Department of Urban Public Health, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

²Department of Family Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

Background: While clinical studies have documented sex differences in emotional, behavioral, and cognitive function of children with Attention Deficit and Hyperactive Disorder (ADHD), it is unknown if these sex differences are due to differences in referral and diagnosis or if they can be also seen when we screen a community sample for ADHD. If these sex differences exist in populations with a diagnosis history but cannot be seen in screening, then they are unfair, preventable, and due to gender (social processes in referral and diagnosis) rather than sex.

Aim:Using the data from a community sample of 9-10-year-old healthy developing children, we explored sex differences in the associations between cognitive, emotional, behavioral, and health status with positive screening vs. history of diagnosed ADHD.

Methods: The Adolescent Brain Cognitive Development (ABCD) study included a national sample of 10,171 American children between ages 9 and 10 years old. This sample included 1,488 children with a history of psychiatric diagnosis and 8,683 children without a diagnosis. The two independent variables were screening and history of ADHD. The following variables were outcomes: symptom severity, cognitive function, body mass index (BMI), internalizing, externalizing, and total behavioral disorders. Sex was the moderator, and age, race, ethnicity, education, household income, and family structure were covariates. Mixed-effects regression models were used to adjust for the nested nature of the data.

Results: Positive screening for ADHD and a history of diagnosis were both associated with worse cognitive function, higher internalizing, externalizing, total problem behaviors, higher inattention (ADHD symptoms), and lower BMI. Sex altered the association between history of diagnosis but not positive screening for ADHD with externalizing, and total behavioral problems as well as cognitive function. Sex did not affect the associations between positive screening for ADHD or a history of diagnosis with BMI or ADHD symptoms. Both history of diagnosis and positive screening for ADHD were associated with higher internalizing for boys than girls.

Conclusion: History of diagnosis, but not positive screening for ADHD, is differently associated with behavioral and cognitive performance of males and females. As sex differences are seen in correlates of history of diagnosis but not positive screening, some of the observed sex differences are due to differential referral and diagnosis rather than differential presentation of ADHD in the community. This finding suggests that some of the so-called “sex differences” that are believed to be due to biology and heritable may be “gender differences” and modifiable. This is important because while gender differences are preventable and modifiable, sex differences are not.

David J Wang^1*, Manas Sharma²

¹Department of Medical Imaging, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, Canada

²Department of Medical Imaging, University Hospital, London Health Sciences Centre, 339 Windermere Road, London, Canada

Peka Christova^1,2, Lisa M. James^1,2,3, Adam F. Carpenter^1,4, Scott M. Lewis^1,4, Rachel A. Johnson¹, Brian E. Engdahl^1,2,5, Apostolos P. Georgopoulos^1,2,3,4*

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

³Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁴Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁵Department of Psychology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Independent lines of research have documented elevated peripheral inflammation and brain white matter alterations in Gulf War Illness (GWI). We recently documented an association of C-reactive protein (CRP), a marker of inflammation, and decreased fornix white matter integrity in GWI. The aim of the present study was to extend those findings to evaluate the association between CRP and white matter anisotropy and diffusion throughout the brain in GWI. Sixty-three veterans with GWI provided blood samples for evaluation of CRP and underwent a 3T magnetic resonance imaging scan from which fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were obtained. An additional index characterizing the shape of the diffusion ellipsoid, Ca, which reflects deviation from sphericity (or isotropy) was obtained. Results demonstrated that CRP was significantly associated with decreased FA and Ca and with increased RD and MD, but not AD. These findings documenting a highly significant association between peripheral inflammation and specific white matter alterations in GWI are discussed in terms of GWI-related exposures that may promote systemic inflammation and deleterious neural effects downstream.

Lisa M. James^1,2,3, Apostolos P. Georgopoulos^1,2,3,4*

¹Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

²Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

³Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁴Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Dementia and Parkinson’s disease are the two most common age-related neurodegenerative conditions. Recent studies have identified Human Leukocyte Antigen (HLA) Class II DRB1 alleles that are protective or neutral with respect to dementia. Here we extend those findings to evaluate the association of the population frequency of HLA DRB1 alleles with the prevalence of dementia and Parkinson’s disease in14 Continental Western European countries. Nine HLA DRB1 alleles were identified including four that are protective against dementia (DRB1*01:01, DRB1*04:01, DRB1*13:02, DRB1*15:01), three that are neutral (DRB1*03:01, DRB1*07:01, DRB1*08:01), and two susceptibility alleles (DRB1*11:01, DRB1*04:05). Results demonstrated that the population prevalence’s of dementia and Parkinson’s disease are highly correlated and that the association between the nine DRB1 alleles above and the population prevalence of dementia is highly overlapping with that of Parkinson’s disease. These findings suggest a common HLA Class II DRB1 profile. Given the diverse role of HLA Class II alleles in protection from foreign antigens, autoimmunity, and, possibly, neuroprotection, the shared HLA profile between dementia and Parkinson’s disease indicates that common immunogenetic mechanisms underlie the pathogenesis and manifestation of these diseases.