All Articles

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.

Don R. Thorpe^1,2, Brian E. Engdahl^1-4, Arthur Leuthold^2,3, Apostolos P. Georgopoulos^1,2,3,5,6*

¹Graduate Program in Cognitive Science, University of Minnesota, Minneapolis, Minnesota, USA

²Brain Sciences Center, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA

³Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA

⁴Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA

⁵Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA

⁶Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA

Mild traumatic brain injury (mTBI) affects 22% of U.S. service members returning from Afghanistan and Iraq. Its diagnosis is challenging due to the heterogeneous structural and functional alterations inflicted by diverse injury mechanisms. mTBI is diagnosed mainly based on history (trauma) and clinical evaluation, since conventional neuroimaging methods, such as magnetic resonance imaging (MRI) and computerized tomography (CT) of the brain, typically do not reveal clear abnormalities. Similarly, the assessment of recovery following mTBI relies exclusively on clinical evaluation, based on several criteria. With respect to brain function, we hypothesized that mTBI reflects disturbed dynamic interactions among neuronal populations, a disturbance not detectable by the aforementioned techniques. In a quest for an objective tool to detect the presence of mTBI and assess recovery from it, here we used magnetoencephalography (MEG), a modality highly suited to assess the dynamic functional status of the brain. Specifically, we used the Synchronous Neural Interactions (SNI) test to evaluate functional brain status of 257 healthy (“control”) veterans, 19 veterans with a clinical diagnosis of active mTBI (“a-mTBI”), and 18 veterans who suffered from mTBI and, at the time of testing, were deemed to have recovered from it (“r-mTBI”). A stepwise linear discriminant analysis (LDA) yielded 37 SNI predictors that classified 100% correctly of all 257 control and 19 a-mTBI brains. We then used these predictors to classify the 18 r-mTBI brains to control or a-mTBI groups: 9 brains (50%) were classified as control, whereas the other 10 (50%) were classified as a-mTBI. These findings (a) document the power of SNI MEG to correctly detect a-mTBI, and (b) raise concerns regarding the validity of clinical assessment tools to pronounce recovery from mTBI. On the positive side, our results provide an objective brain-based continuum along which the status of a mTBI brain can be assessed. This measure, together with clinical evaluation, should appreciably reduce the uncertainty and considerably improve the quantification of recovery from mTBI, guiding further treatment.

Caroline Figueiredo da Silva¹*, Gustavo Figueiredo da Silva¹, Washigton Luiz Gomes de Medeiros Junior¹, Marcus Vinícius Magno Gonçalves²

¹Medical student - Department of Medicine, University of the Region of Joinville (UNIVILLE), Brazil

²Medical Doctor, PhD and Professor of Neurology, University of the Region of Joinville (UNIVILLE), Brazil

The objective of this review is to provide an overview of the current knowledge of Anti-IgLON5 syndrome. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 is crucial for the Anti-IgLON5 Syndrome diagnosis. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent, and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at the hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata, and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. Early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The Anti-IgLON5 syndrome mortality is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends on some clinical and analytical characteristics. In addition, future studies are needed to thoroughly analyze the aspects of pathogenesis and treatment of this important pathological syndrome.

Abbreviations

CNS - Central Nervous System

CSF - Cerebrospinal Fluid

IgG - Immunoglobulin G

MRI – Magnetic Resonance Imaging

PSP-like - Progressive Supranuclear Palsy

p-Tau - Hyperphosphorylated Tau Protein

REM - Rapid Eye Movement

Peka Christova^1,2, Lisa M. James^1,2,3, Adam F. Carpenter^1,4, Scott M. Lewis^1,4, Brian E. Engdahl^1,5, 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 demonstrated that GWI is associated with elevated inflammatory markers, metabolic disruptions, and alterations in brain morphometry. Possessing specific Class II human leukocyte antigen (HLA) alleles, on the other hand, has been shown to protect against GWI and to be inversely associated with symptom severity in a dose-dependent manner. The aim of the present study was to evaluate the association between C-reactive protein (CRP), a marker of inflammation, body mass index (BMI), and brain morphometry in GWI veterans with and without a protective HLA allele. Sixty-three veterans with GWI provided blood samples for evaluation of CRP and HLA, height and weight for calculating BMI, and underwent a 3T magnetic resonance imaging scan from which the volume, surface area, and cortical thickness of 68 cortical regions of interest (ROI) were determined. Results demonstrated that the CRP was highly significantly associated with BMI and cortical thinning in veterans lacking protective HLA alleles but not in those possessing a protective HLA allele. Given the role of HLA in antibody production against foreign antigens, the findings suggest that persistent foreign antigens stemming from lack of immunogenetic protection against them contribute to inflammation, metabolic disruption, and cortical thinning in GWI. The findings are discussed in terms of GW-related exposures that are known to result in inflammation.

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, US

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

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

Memory and mood impairments are among the most commonly reported symptoms in veterans with Gulf War Illness (GWI), suggesting hippocampal involvement. Several studies have also documented evidence of inflammation in GWI. The aim of the present study was to evaluate the association between C-reactive protein (CRP), a marker of inflammation, and hippocampal volume and microstructural alterations of its major output, the fornix. Sixty-three veterans with GWI provided blood samples for evaluation of CRP and underwent a 3T magnetic resonance imaging scan from which hippocampal volume and fornix fractional anisotropy (FA) were obtained. Results demonstrated that CRP was significantly and negatively associated with hippocampal volume and fornix FA in GWI. Given the known closely interwoven associations between inflammation and neurodegeneration, it is possible that the effects we observed could be due to neurodegeneration, secondary to chronic neuroinflammation. Finally, given the known association of hippocampus to memory and mood disorders, our findings provide new insights into memory and mood alterations associated with GWI.

Keshav Mishra¹, Devendra Purohit¹*, Somnath Sharma¹

¹Department of Neurosurgery, SMS Medical College, Jaipur, India

Cognitive impairment is a major cause of morbidity and impaired quality of life in traumatic brain Injury (TBI) patients. Assessment of cognitive function using classically designed scales is time and resource intensive undertaking which also requires expert neuropsychiatrist referral. Montreal cognitive assessment Score (MoCA) is a brief screening tool designed to assess various cognitive domains which has been found to be more sensitive than Mini Mental State Examination (MMSE) score both in Alzheimer disease and subsequently in TBI population. Applied on TBI population, it reliably detects cognitive impairment in mild TBI, compared to normal controls and also differentiates cognitive disturbances between mild and severe TBI but its ability to differentiate cognitive function between mild and moderate TBI is equivocal.

Maria del Rocio Cantero, Horacio F. Cantiello

Laboratorio de Canales Iónicos, Instituto Multidisciplinario de Salud, Tecnología y Desarrollo (IMSaTeD, CONICET-UNSE) Santiago del Estero, Argentina

Microtubules (MTs) are long cylindrical structures of the cytoskeleton that control cell division, vesicular transport, and the shape of cells. MTs are highly charged and behave as nonlinear electrical transmission lines. However, comparatively little is known about the role(s) these nonlinear electrical properties of MTs play in cell function. MTs form bundles, which are particularly prominent in neurons, where they help developmentally define axons and dendrites. The present review summarizes recent work from our laboratory which demonstrated that 1) bundles of rat brain MTs spontaneously generate electrical oscillations and bursts of electrical activity similar to action potentials; 2) actin filaments control electrostatically the oscillatory response of brain MTs; and 3) neurites of cultured mouse hippocampal neurons generate and propagate electrical oscillations thus, providing a cellular correlate to the isolated MT oscillations. Electrical oscillations are an intrinsic property of brain MT bundles, which may have important implications in the control of various neuronal functions, including a contribution to the intrinsic oscillatory modes of neurons, and thus to higher brain functions, including the formation of memory and the onset of consciousness.

Yu-Lung Lin¹, Yi-Wei Li¹, Li-Na Wei¹*

Department of Pharmacology, University of Minnesota, Minneapolis, USA

Receptor interacting protein 140 (RIP140), gene named Nuclear receptor interacting protein 1 (Nrip1), is a transcription co-regulator of numerous nuclear receptors and transcription factors that are important for various biological processes. RIP140 is highly expressed in various cell types of the brain, especially cortex and hippocampus. Increasingly, studies have begun to reveal its multiple functional roles in maintaining brain health. In particularly, there appears to be an intimate relationship between RIP140 and neurodegenerative diseases, such as reduced RIP140 expression in Alzheimer’s Disease (AD) postmortem brain and impaired cognitive functions in RIP140 knockout mice. The different functional roles of RIP140, mediated by distinct mechanisms, coordinately contribute to the execution of stress response of the brain to Endoplasmic Reticulum (ER) stress, heat shock (HS) stress, oxidative stress and psychological/behavioral stress. In this review, we describe the roles of RIP140 in three brain cell types (neurons, microglia, and astrocytes) stressed by pharmacological agents or behavioral manipulation. These results demonstrate physiological integration of various functional roles of RIP140 in different brain cells to facilitate survival and recovery from stress. The results also suggest a potential, preventive and/or therapeutic strategy by targeting RIP140 in managing neurodegenerative diseases.

Steven Yale¹*, Halil Tekiner², Eileen S Yale³

¹University of Central Florida College of Medicine, Department of Internal Medicine, Orlando, USA

²Department of the History of Medicine and Ethics, Erciyes University School of Medicine, Melikgazi, Kayseri, Turkey

³University of Florida, Division of General Internal Medicine, Gainesville, USA

Alain L. Fymat*

International Institute of Medicine & Science, California, U.S.A

A variety of radiological imaging techniques are used singly or in combination to diagnose and treat neurodegenerative diseases. Their respective roles are reviewed and discussed within the contexts of Alzheimer's disease and Parkinson's disease. In Alzheimer's, MRI and PET scans are usually employed to rule out confounding symptoms from other disorders/diseases and to assess the extent of brain atrophy as the disease progresses. In Parkinson's, CT and MRI are not very informative but can rule out secondary causes of Parkinsonism; 3T-MRI is still under evaluation notwithstanding its high sensitivity and specificity; and PET and SPECT can rule out drug-induced Parkinsonism but are not reliable in distinguishing Parkinson's from other neurodegenerative causes of Parkinsonism. Functional SPECT/ DaTscan is indicated for detecting loss of functional dopaminergic neuron terminals in the striatum of patients with clinically uncertain Parkinsonian syndromes in order to help differentiate essential tremor, multiple system atrophy, and progressive supranuclear palsy from Parkinson's but is unable to discriminate between them. However, DaTscan can help differentiate dementia with Lewy bodies from other forms of dementia. Because of its importance in Parkinson's, the complementary technology of magnetic resonance-guided high-intensity focused ultrasound is also reviewed and compared to electromagnetic brain stimulation and radiosurgery.

Abbreviations

AAD: Alzheimer's Disease; ALS: Amyotrophic Lateral Sclerosis; APP: Amyloid Precursor Protein; CNS: Central Nervous System; CT: Computed Tomography; DBS: Deep-Brain Stimulation; EMBS: Electromagnetic Brain Stimulation; ET: Essential Tremor; fGCA: Frontal Cortical Atrophy; fMRI: functional MRI; HD: Huntington's Disease; HIFUS: High-Intensity Focused Ultra-Sound; MRI: Magnetic Resonance Imaging; MRT:Magnetic Resonance Thermometry; MSA: Multiple System Atrophy; MTA: Medial Temporal lobe Atrophy; NDD: Neurodegenerative Disorder; PA: Posterior Atrophy; PD: Parkinson's Disease; PET: Positron Emission Tomography; PS: Parkinson's Syndrome; PSP: Progressive Supranuclear Palsy; RS: Radiosurgery; SPECT: Single Photon Computed Tomography; US: Ultrasound; VIN: Ventral Intermediate Nucleus.

Isabelle Pastor Bandeira¹*, Washigton Luiz Gomes de Medeiros Junior¹, André Eduardo de Almeida Franzoi¹, Laura Fiuza Parolin², Paulo Roberto Wille³, Marcus Vinícius Magno Gonçalves⁴

¹Department of Medicine, University of the Region of Joinville (UNIVILLE), Brazil

²University of the Region of Joinville (UNIVILLE), Brazil

³University of the Region of Joinville (UNIVILLE), Brazil

⁴University of the Region of Joinville (UNIVILLE), Brazil

Pseudoathetosis is a movement disorder caused by loss of proprioception. The disorder is characterized by involuntary, slow, and writhing movements. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The disease is characterized by multiple lesions of the brain and spinal cord. These lesions are disseminated in time and space. The onset of the neuroinflammation is characterized by episodes of neurological dysfunction that usually recover. Reports of MS with pseudoathetosis are extremely rare. The association of these two disorders is uncommon. This article shows a 29-year-old woman who presented pseudoathetosis as the initial symptom of MS. Therefore, this case report is very relevant for medical knowledge due to the rare form presentation of MS.

Mohamed ElSayed Abdelhady¹*, Nida Fatima²*, Yaman Al Kailani¹, Ahmed Own¹, Surjith Vattoth¹

¹Department of Neuro radiology, Hamad General Hospital, Doha, Qatar

²Department of Neurosurgery, Hamad General Hospital, Doha, Qatar

Loris A Chahl

School of Biomedical Sciences and Pharmacy University of Newcastle NSW 2308 Australia

It has been shown previously that rats treated as neonates with capsaicin exhibited hyperactivity in a novel environment and had brain changes, including reduced brain weight, reduced hippocampal area, reduced cortical thickness and increased neuronal density in several cortical areas. These brain changes resembled those found in subjects with schizophrenia. This mini review discusses recent findings on the effects of capsaicin on hippocampal neurons and the role of TRPV1 channels in the central nervous system, which provide a possible explanation for the effects of capsaicin on the developing rat brain. Future studies on the role of TRPV1 channels in the brain hold great promise for further understanding of neuropsychiatric disorders.

Tao Tao*, Jie Sun, Min-Sheng Zhu

Model Animal Research Center, State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing University, China

Ashutosh Gupta

Consultant Neurologist, Department of Neurology, Shree Aggarsain International Hospital, Rohini, Delhi, India

The venom toxins of honeybee cause anaphylactic allergic reactions and/or any type of stroke. Hemorrhagic strokes are more severe than the ischemic strokes. Diverse pathophysiological mechanisms have been postulated for occurrence of these strokes. We discuss here mechanism of acute fatal hemorrhagic and ischemic stroke in a middle age woman, stung by the honeybee on her right arm and who clinically manifested loss of consciousness and tonic clonic seizure, within 3-4 hours followed by hemiparesis. The MRI revealed brain lesions of multiple infarctions with hemorrhagic transformation, subdural (SDH) and subarachnoid (SAH) hemorrhages. This appears to be the first report, wherein a patient had entire spectrum of stroke (infarcts, subarachnoid and subdural hemorrhages), after a single inciting event of bee sting.

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

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

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

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

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

⁵Department of Neurology, University of Minnesota Medical School, Minneapolis, USA

Human Leukocyte Antigen (HLA) Class II DRB1*13:02 has recently been found to protect against dementia in Continental Western Europe. Here we extend those findings by evaluating the association between the population frequency of two additional Class II HLA alleles – DRB1*01:01 and DRB1*15:01 – alone and in combination with DRB1*13:02, on dementia prevalence in Continental Western Europe. Results indicated that the prevalence of dementia in 14 Continental Western European (CWE) countries significantly decreased exponentially with increasing frequency of any of the three alleles alone and in combination (P’s < 0.001). When combined, the population frequency of the three alleles accounted for 67% of the variance in dementia prevalence. The combined frequency of DRB1*01:01, DRB1*13:02, and DRB1*15:01 was also significantly associated with dementia prevalence in those aged 65 years and older (P = 0.004) and with a change in dementia prevalence between 1990 and 2016 (P = 0.006). These findings, which document the protective effects of three common Class II HLA alleles on dementia prevalence in CWE, are discussed in terms of the role of HLA class II genes in pathogen elimination. More specifically, we hypothesize that dementia prevalence is higher for countries in which the population frequency of these protective alleles is low, prohibiting the successful elimination of pathogens that may play a causal role in dementia.

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

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

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

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

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

Dementia is a leading cause of death worldwide, representing a significant global burden. In addition to genetic and lifestyle factors that have been widely linked to dementia, pathogens are increasingly recognized as contributing to the development of dementia. Here we discuss the role of human leukocyte antigens (HLA) in maintaining brain health by facilitating the elimination of pathogens and highlight evidence suggesting that the inability to eliminate pathogens contributes to dementia. Finally, we briefly review common forms of dementia including Alzheimer’s disease, vascular dementia, frontotemporal dementia, Lewy body dementia, and prion dementia in an effort to contextualize the role of persistent pathogens across the various dementia phenotypes.