- McMaster University, Canada
- Title:Pathogenesis of Neurotrauma in the Model of Spinal Cord Injury with Future Directions of Neuroprotective Therapies
- Time :
Spinal cord injury (SCI), traumatic brain injury (TBI) and stroke constitute the most important human diseases with no effective treatments which is related to the lack of understanding of the pathogenesis of the disease initiated by the traumatic (SCI, TBI) or by vascular (stroke) events. In the rat model of SCI studied systematically, 3 supervening phases are evident; (1) Acute Phase, lasts 2 days and is characterized by hemorrhage, poorly defined areas of cellular necrosis and edema; (2) Inflammatory Phase, begins on the day 3 with infiltration of the areas of hemorrhage and necrosis by large numbers of M1 type macrophages phagocytizing myelin and red blood cells. Depending on the location of the hemorrhagic necrosis in the injured spinal cord, there are 2 types of inflammation; (i) areas deep in the spinal cord are converted within the 1st week into a cavity of injury (COI) encompassing necrotic debris and fluid infiltrated by M1 macrophages; (ii) in superficial areas granulomatous infiltration from the subarachnoid space including macrophages, fibroblasts and blood vessels form arachnoiditis obliterating the spinal cord. Both COI and arachnoiditis are walled off by progressively severe astrogliosis mounted by the surrounding spinal cord. The severity of M1 macrophage infiltration in the COI peaks at 1-4 weeks and then slowly declines but small numbers are still present at 16 weeks post-SCI. (3) Resolution Phase overlaps with Inflammatory Phase by 12 weeks and leads to formation of mature syrinx from the COI. Arachnoiditis becomes a mature scar devoid of glial cells and macrophages. The unusual severity and extraordinarily long course of inflammation initiated by trauma in the spinal cord is related to locally massive damage to myelin sheaths, a potently immunogenic material. Its phagocytosis by M1 macrophages is associated with their activation and presence of elevated factors of inflammation such as TNF-, IL-1, IFN-, Il-6, chemokines, MMP-8, within the 1st week and their decline in levels later. The lack of M1 to M2 macrophage polarization in COI with concurrent decline in numbers of M1 macrophages during the Resolution Phase suggests that classic immune mechanisms do not play role in inhibition of severity of inflammation but rather the spinal cord tissue reaction, specifically astrogliosis does. This is supported by previous observations on the SCI in the Long Evans Shaker (LES) rat where inflammation is entirely eliminated by 7 days post-trauma. The severity of inflammation in COI with active myelin phagocytosis by M1 macrophages beyond 16 weeks indicates continuous destruction of the surrounding spinal cord and calls for anti-inflammatory treatments to provide neuroprotection beyond trauma. Since the spinal cord reaction confines the inflammation to the COI which is directly connected to the subarachnoid space, infusion of anti-inflammatory drugs; dexamethasone, Serp-1 and M-T7, immunomodulatory proteins derived from Myxoma virus, into the subdural space resulted in reduction of the numbers of macrophages by 50-80%. While dexamethasone was effective in lowering the numbers of macrophages, it was unduly toxic but both Serp-1 and M-T7 were well tolerated by recipient rats. However, when infused intraperitoneally, both proteins had little (M-T7) or no detectable (Serp-1) effect on the levels of infiltrating macrophages in the COI indicating that constant subdural infusion is an effective mode of administration and intravenous administration is not. Importantly, 1 week long infusion reducing numbers of macrophages resulted in persistence of large amounts of un-phagocytized, myelin-rich necrotic debris and numerous red blood cells that would lead to re-igniting of the severe inflammation at the premature termination of anti-inflammatory treatment. Therefore, a much longer than 1 week, subdural infusion needs to be administered to eliminate inflammation and its destructive activity following SCI and also TBI and stroke involving white matter injury.
Dr.Jacek M. Kwiecien completed his DVM (Doctor of Veterinary Medicine) in 1983 from University of Agriculture in Lublin, Poland. He gained his MSc in 1991 from University of Guelph, Canada. He received his PhD in Veterinary Pathology in 1995 from University of Guelph, Canada. He completed his Post-Doc in Veterinary Pathology from 1994-1996 in University of Wisconsin-Madison, USA, Fellow National Multiple Sclerosis Society, USA.
His current Status is: HE is an Associate Professor of Department of Pathology and Molecular Medicine in McMaster University, Canada. He is also one of the Veterinary Research Pathologists in McMaster University.
His research Interests: Pathogenesis of neurotrauma
Animal models of spinal cord injury and of traumatic brain injury
Neuroprotective treatments in neurotrauma
Mechanisms involved in neuroregeneration.
- Medical University of Varna, Bulgaria
- Title:In Vitro Model of Ischemic Stroke: Ghrelin and Potential Intracellular Factors Preventing the Secondary Brain Damage and Ameliorating Postischemic Recovery
- Time :
Normal brain function is highly dependent on oxygen supply, and one of the first consequences of ischemia is change in the neural network: acute episodes of hypoxia result in decreased synaptic activity, while the longer periods of oxygen deprive cause neuronal dead. Ischemic stroke, which usually results from cerebral arteries occlusion, leads to neuronal dead in the infarction core. Stroke is the second leading cause of dead above age of 60 years. Annually, 15 million people worldwide suffer a stroke, nearly six million die, and another five million get permanently disabled. Unfortunately, effective specific therapy for the ischemic brain damage is lacking. However, many patients improve in different period of time following stroke, inferring an innate capacity for brain repair. The exact mechanisms of this recovery are not clear but they may include synaptogenesis and adult neurogenesis. To test this hypothesis we used dissociated cortical neurons as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin (Ghr) treatment. Briefly, cultures were exposed to hypoxia for 6 h (pO2 lowered from 150 to 20 mm Hg). Three hours after the re-oxygenation, half of the cultures were treated with Ghr for 24 h, while the other, non-supplemented, were used as a control. All cultures were stained immunocytochemically for detection of the synaptic marker synaptophysin. Hypoxia led to drastic decline of the number and the activity of synapses, followed by partial recovery after return to normoxia, but still below the pre-hypoxic level. Ghr treatment significantly increased synapse density and activity, as compared with the controls or with the pre-hypoxic period. In addition, we investigated the effect of Ghr on the expression of some intrinsic cellular factors important for the regulation of neurogenesis – Pax6 and Zbtb20. Hypoxia reduced the percentage of cells expressing Pax6 and Zbtb20, but Ghr administration during re-oxygenation considerably upregulated their expression. Furthermore, significant number of Pax6-positive cells had features consistent with neuroepithelial/progenitor cells phenotype, which we normally do not observe in mature cultures under normoxic conditions. In conclusion, Ghr stimulates neuronal network connectivity and activity after hypoxia exposure, and activates some endogenous factors promoting neurogenesis in mature neuronal networks in vitro. Though the functional impact of postischemic neurogenesis is yet unknown, it might be a prospective therapeutic target for stroke patients.
Dr. Irina I. Stoyanova–van der Laan graduated in General Medicine at the Medical Academy, Sofia, Bulgaria and specialized at human anatomy and histology. In 1983 she was appointed as an Assistant Professor and later on, in 2004, as an Associate Professor at the Department of Anatomy, Trakia University, Bulgaria. She obtained her PhD in 2002 (thesis “Morphological and neurochemical characteristics of certain primary sensory neurons”). In 2008-2015 she worked as a postdoc at the department of Biomedical Signals and Systems, and the department of Clinical Neurophysiology, University of Twente, the Netherlands. In 2011 she was appointed as an Associate Professor in Human Anatomy and Physiology at the University College Roosevelt, the Netherlands. Since 2015 she is an Associate Professor at the department of Anatomy and cell biology, Medical University, Varna, Bulgaria.
Her research interests are: Neurosciences: different aspects of the structural and functional neuromorphology and their clinical implications. For her achievements she was awarded twice (at International Falk Foundation Symposium of Gastroenterology in Bucharest, Romania, 2000, and at 7th International Symposium on Cytokines and Chemokines (satellite of the 13th World Congress of Gastroenterology), Montreal, Canada, 2005). She is also a member of the editorial boards of two international journals – International Journal of Biomedical Sciences (since 2005), Adipobiology (since 2009), and a reviewer for other scientific journals.
- University of Haifa, Israel
- Title:Understanding the Variability of Vulvar Pain Manifestation: The Manifestation of Neuropathic Pain Symptoms in Provoked Vestibulodynia
- Time :
Provoked vestibulodynia (PVD), is the common chronic pain syndrome characterized by severe pain and tenderness on vestibular touch or attempted vaginal entry during sexual intercourse (dyspareunia). The incidence of PVD is estimated as 12%-16%, but the actual incidence is presumably higher than reported. The etiology of PVD is considered multifactorial, however, no single causative factor has yet been identified. Current efforts to subdivide PVD into sub-groups had led to the allocation of patients into primary and secondary forms of PVD, describing the onset of symptoms in regards to timing of first provoking physical contact. The comparison between these two types demonstrates pain-related personality features, mainly higher anxiety, among primary PVD patients as well as greater neural hypertrophy in the vestibular tissue as compared to those with secondary PVD. However, this distinction does not address mechanism-based etiology and consequently fails to establish diagnostic and treatment guidelines. Despite that the possible role of neuropathic alterations has been suggested, the precise mechanisms of such idiopathic pain disorder is still insufficiently clear. Treatments focus mainly on the pain and its effect on sexual functioning, but wide disparity in treatments efficacy is reported among PVD patients.
This presentation will focus on the notion that several distinctive sub-groups of PVD exists, such that the anatomic location of provoked vestibular pain hypersensitivity and it’s associated with specific features represent different etiological mechanisms in PVD. Data abstained from large sample of PVD patients will be presented to address whether in part of the women, vestibular pain location (circumferential or posterior vestibule alone) and the existence of vulvar allodynia/hyperalgesia and/or general pain-hypersensitivity represent neuropathic changes. Pain response to experimental stimulation (Q-tip and pressure stimuli) and self-reported pain measures (tampon insertion and penetrative intercourse) will serve to reveal whether vestibular neuroproliferation result painful intercourse. The possibility that congenital or acquired neuronal sensory alteration will be discussed form embryologically perspective in which the endodermal neuroproliferation associated with local and systemic pain sensitivity. This presentation will also highlight whether psychosocial features, sexual functioning and cognitive factors such as pain catastrophizing involved in the manifestation of vulvar pain experience. Identifying sub-groups of PVD based on the mucosal and neuropathic changes may allow better understanding about pain variability in women who suffer from chronic pelvic pain and promote individualized management.
Dr. Michal Granot is an associate professor at the Faculty of Social Welfare & Health Sciences, Department of Nursing, the University of Haifa, Israel. Her clinical background has shaped her research activity that focuses mainly on psychophysical assessment of pain modulation processing. As part of a multi-disciplinary team at the Laboratory of Clinical neurophysiology at the Technion and Rambam Medical Campus she investigates psychological, neurophysiological and cognitive features that affect pain perception and modulation in acute and chronic pain conditions, with special emphasis on pain disorders among women, such as chronic pelvic pain. She has been a co-Principal investigator in several research projects that focused on pain variability and the mechanisms that are involved in the transition from acute to chronic pain, using lab tests of pain induced by experimental stimulations combined with pain related personality questionnaires.
- The Scripps Research Institute and Protego Biopharma, USA
- Title:Treating Protein Aggregation Diseases in the Central and Peripheral Nervous Systems: Success and Failure in Familial Amyloidotic Polyneuropathy and Alzheimer’s disease
- Time :
It was clear almost from the first descriptions in Portugal that the hereditary autonomic and peripheral neuropathy endemic in Povoa de Vazim was due to amyloid deposits in peripheral and autonomic nerves. It remained only for the precursor to be identified as transthyretin (TTR) and the mutation characterized. We now know that there are 123 different mutations in the coding region of the protein that are associated with autosomal dominant neuropathic and/or cardiomyopathic syndromes and that without aggregation there is no clinical disease. Over the last two decades therapies directed at reducing or eliminating amyloid formation by reducing the availability of the TTR aggregation substrate have been introduced into clinical practice. Hence liver transplantation, small molecule molecular stabilizers of TTR and oligonucleotide therapies have reduced symptoms and prolonged life for the carriers of the mutations, a major advance in neurologic patient care. Nonetheless, cure has not been achieved and a significant proportion of the patients do not respond to the available therapies, representing a still unmet medical need.
The role of amyloid deposits in the pathogenesis of Alzheimer’s disease, from the very beginning, was far more contentious with the uncertain role of amyloid articulated initially by Hardy and Higgins and then by Hardy and Selkoe in the titles of their seminal papers e.g. “Alzheimer’s disease: the amyloid cascade hypothesis”. The generation of mice transgenic for mutant forms of the Aβ precursor or the mutant enzymes involved in processing AβPP in the autosomal forms of the human disease allowed the development of therapeutics based on blocking the generation of the amyloid precursor or the aggregation of the amyloidogenic peptide. Enzyme inhibitors tested in these models, as well as antibodies directed against the peptide, its oligomers or fibrils, moved from blocking the pathologic changes seen in the transgenic mouse brains to large scale clinical trials. In contrast with the findings in TTR-associated FAP, the results have been disappointing. We now await the results of trials using secretase inhibitors and/or antibodies in subjects who are carriers of genes that produce autosomal dominant AD administered well before the onset of disease, as judged by the age of onset characteristic of their kindred. The results of such trials will provide the final test of the Aβ hypothesis.
Dr. Buxbaum’s laboratory at NYU School of Medicine identified TTR mutations responsible for both autosomal dominant polyneuropathic and cardiomyopathic forms of amyloidosis and developed transgenic mouse models of systemic TTR deposition. At The Scripps Research Institute he continued his extensive clinical and genetic characterization of the cardiomyopathic TTR mutation that is highly prevalent in African Americans. He served as consultant to Foldrx during its development of tafamidis (Vyndaqel, Pfizer). More recently his group has studied the interaction between TTR and Aβ, finding that neuronal production of TTR may have a salutary rather than an adverse effect on the development of Aβ deposits in the brains of both Aβ transgenic mice and humans with AD.
- University of Virginia Health System, USA
- Title:Success Stories Using Emergency Telestroke Services
- Time :
The ability to rapidly access and evaluate acute stroke patients is crucial to ensure a good clinical outcome. Time sensitive therapies, including intravenous thrombolytics (tissue plasminogen activator) and thrombectomy endovascular techniques in selected patients can improve outcome by ~30-70% versus no treatment. Telestroke, the use of live remote videoconferencing by a neurologist to distance emergency departments has allowed greater access and expertise in decision making to render these treatment options. In addition, it allows for higher accuracy in patient selection for treatment, ensuring the right treatment is provided at the right time in the right patient.
We will discuss the current state of Telestroke (international) programs, highlighting the successes, and elucidating the remaining barriers and future growth needs in the field. Clinical cases will be presented to illustrate the new neuroimaging techniques in the field (“RAPID” software brain mapping), and endovascular technical advances (stent-retrievers). Emerging acute stroke therapies, including new thrombolytics being tested, will be discussed. Patient clinical outcomes will be explored in terms of financial, humanistic and societal savings.
Dr. Nina J. Solenski, M.D., FAHA is an internationally recognized vascular neurologist with over 25 years of cerebrovascular clinical and research experience. She completed her medical training at Jefferson Medical College, Philadelphia, PA, and medical and neurology residency training at Dartmouth University, NH and at the University of Virginia (UVA), VA. She completed her Cerebrovascular Fellowship training at the University of Virginia, and was awarded a NIH K08 stroke research grant. She is ABPN board certified in General Neurology and Vascular Neurology. She has been practicing since 1993, specializing in development of telestroke and teleneurology programs, stroke in the young patient, and supporting first generation college students interested in the medical field. She has been involved in over 60 clinical stroke research trials over the years. Current projects include developing a national stroke system of care in the Dominican Republic, implementing a state-wide “ECHO” Stroke program to educate primary care physicians on primary and secondary care of stroke patients. She recently was selected for the prestigious American Academy of Neurology “Women in Neurology Leadership” and has served both as the Chair of the UVA Faculty Senate and as faculty representative on the University of Virginia’s corporate Board of Visitors.
- The first Affiliated Hospital of Nanchang University, China
- Title:Plasma Trimethylamine N-oxide, A Gut Microbe–Generated Phosphatidylcholine Metabolite, is Associated with Autism Spectrum Disorders
- Time :
The compositions of the gut microbiota and its metabolites were altered in autism spectrum disorders (ASD) individuals. The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) in relation to the risk and degree of the severity of ASD.
Dr. Lijuan Quan graduated from the Nanchangl University ,China in 2011, now she is a deputy director of rehabilitation department of the First affiliated Hospital of Nanchang University, Attending and associate chief physician. She serves on the following committees: She is a standing member of the first committee of rehabilitation assessment professional committee of China association for the rehabilitation of disabled persons. She is a member of the third session of child rehabilitation committee of Chinese rehabilitation association, She is a member of the first session of the advisory committee on rehabilitation medicine of the Chinese association of rehabilitation medicine. She is a member of autism spectrum disorders group, child rehabilitation committee, Chinese academy of rehabilitation medicine. She is the Vice President of the second council of jiangxi disabled persons rehabilitation association. She is the Vice chairman of the second committee of autism rehabilitation professional committee of jiangxi disabled persons rehabilitation association. She is the Vice – chairman of child rehabilitation committee of jiangxi rehabilitation medical association. She is a member of the second board of jiangxi rehabilitation medical association.
- University of Cambridge, UK
- Title:Compounding Nimodipine Oral Suspension for Subarachnoid Hemorrhage
- Time :
What happens when there is an entire patient population, not just a specific patient, which cannot take a commercial pharmaceutical product due to significant adverse effects, although the commercial product has a U.S. Food and Drug Administration-approved indication for the medical problem? What should or can be done in this situation? This presentation discusses this dilemma using subarachnoid hemorrhage as an example of a true documented medical need, and discuss the option and circumstances surrounding the compounding of a nimodipine oral suspension, a U.S. Food and Drug Administration-approved indication for the treatment of subarachnoid hemorrhage.
The learning objectives include the following:
Discuss the need for an oral nimodipine liquid.
Provide options for treating patients with subarachnoid hemorrhage.
Provide information on compounding nimodipine oral suspension to avoid adverse effects.
Dr. Mcelhiney is the Team Lead Compounding Pharmacist and a preceptor for Indiana University Health in Indianapolis, Indiana. It is one of the largest health-systems in the United States, consisting of 20 hospitals and dozens of outpatient clinics and surgery centers.She is an author for the International Journal of Pharmaceutical Compounding and contributing author in pharmacy and medical textbooks. Dr. McElhiney is a full fellow in the American College of Apothecaries (ACA), American Society of Health-System Pharmacists (ASHP), and the International Academy of Compounding Pharmacists (IACP). She has served on several national committees and board of directors in professional pharmacy organizations and received several awards. Dr. McElhiney currently serves as the President-Elect for the American College of Apothecaries.Dr. McElhiney earned a B.S. in Pharmacy from Purdue University in 1984. She earned a Pharm.D. (2002) and a Masters (2012) from the University of Florida.
- University of Bologna, Italy
- Title:Field Cancerization Therapy with Ingenol Mebutate Contributes to Restoring Skin-Metabolism to Normal-State in Patients with Actinic Keratosis: A Metabolomic Analysis
- Time :
Actinic keratosis (AK) is a skin premalignant lesion, which progresses into squamous cell carcinoma (SCC) if left untreated. Ingenol mebutate gel is approved for local treatment of nonhyperkeratotic, non-hypertrophic AK; it also has the potential to act as a field cancerization therapy to prevent the progression of AK to SCC. To understand the mechanisms of ingenol mebutate beyond the mere clinical assessment, we investigated, for the first time, the metabolome of skin tissues from patients with AK, before and after ingenol mebutate treatment, with high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS NMR). The metabolomic profiles were compared with those of tissues from healthy volunteers. We identified a number of metabolites, the homeostasis of which became altered during the process of tumorigenesis from healthy skin to AK, and was restored, at least partially, by ingenol mebutate therapy. These metabolites may help to attain a better understanding of keratinocyte metabolism and to unmask the metabolic pathways related to cell proliferation. These results provide helpful information to identify biomarkers with prognostic and therapeutic significance in AK, and suggest that field cancerization therapy with ingenol mebutate may contribute to restore skin metabolism to a normal state in patients with AK.
Dr. Valeria Righi is a researcher at the University of Bologna since 2012. She is professor of biochemistry. Her research activity is focused on metabolomics sciences through the use of nuclear magnetic resonance (NMR). She was involved in the study of cerebral cancer pathologies and the gastrointestinal system cancer diseases. Recently, she has focused her attention on skin diseases (in particular those defined as non-melanoma skin cancer) to the study of tissues and bio-fluids and also to diseases linked to behavioural disorders due to food. Metabolomics is a science that allows us to evaluate metabolic changes even when histological analyses do not detect cellular alterations. She held part of her doctorate and post-doc at the “Instituto de Investigaciones Biomedicas Alberto Sols” Madrid (Spain) and she was post doc at the Harvard Medical School of Boston (USA) in 2008-2009. She was awarded by L’Oreal and Unesco in 2009.
She is author and co-author of over 45 publications in high-impact international scientific journals and has presented numerous works at national and international conferences.
- Virginia Commonwealth University, USA
- Title:Microglia-Axonal Interactions and Diffuse Glial Signatures in a Translational Model of Mild Brain Trauma
- Time :
Traumatic brain injury (TBI) is a highly prevalent disease with devastating costs associated with long term morbidity. While this morbidity has been linked to diffuse pathologies, our knowledge regarding these TBI-initiated diffuse pathologies is limited. Further, there are currently no successful therapeutics to treat TBI, despite many promising candidates. The unsuccessful clinical translation of many promising therapeutics has triggered a call for the use of higher-order animal models prior to transitioning to large-scale clinical trials. Due to their high level of homology with humans in terms of systemic inflammatory responses, metabolic rates, and cytoarchitecture, we utilize an adult micro pig model to study the effects of mild TBI in a more translational fashion. Additionally, as thalamic damage has been suggested to play a central role in the pathogenesis of mild TBI and its various symptoms, we focus much of our investigations on the thalamic domain. In this talk we will explore the association between diffuse axonal injury and neuroinflammation, specifically investigating activated microglial process convergence onto injured axonal segments following diffuse brain injury as well as the species variation we have observed in this trauma-induced phenomenon. We will also explore histopathological signatures associated with serum biomarkers in a micro pig model of diffuse traumatic brain injury. These studies were initiated as part of the multi-institute Operation Brain Trauma Therapy (OBTT) consortium.
Dr. Audrey Lafrenaye, P is an Assistant Professor in the Department of Anatomy and Neurobiology at Virginia Commonwealth University (VCU), USA. Her background is in cellular and molecular neuroscience, with focuses on quantitative immunohistological approaches, glial pathology (including microglia, astrocytes and oligodendrocytes), and traumatic brain injury (TBI). Her research is currently funded by the National Institutes of Health and focuses on evaluating the progression and molecular mechanisms involved in diffuse neuronal and glial pathologies following TBI. She is also a site-PI for the Operation Brain Trauma Therapy (OBTT) pre-clinical therapeutic and serum biomarker discovery consortium, which is the only pre-clinical multi-institute consortium of its type in the field. She is an active member of the National Neurotrauma Society and Training, Education and Mentoring in Neurotrauma for the promotion of diversity in neurotrauma research.
- Capital Medical University, China
- Title:Accessory Nerve Schwannoma: A New Case Report and Systematic Review
- Time :
Background and Objective: Accessory nerve schwannoma is an exceedingly rare disease. It has not yet been well characterized because of the rarity of this disease. We sought to expend the knowledge of accessory nerve schwannoma by reviewing comprehensive literature and adding to it a new case that is originated from spinal root of accessory nerve at the cerebellomedullary cisterna.
Case description: A 62-year-old woman presented with a 1-month history of the right occipital pain. There were no apparent neurologic deficits in physical examination. A brain Magnetic Resonance image found a well-demarcated mass at the right cerebellomedullary cistern, extending to the cervical 1 level and moderately compressing the medullar oblongata. The mass was completely removed via a right suboccipital craniotomy with cervical 1 laminectomy. A brain Magnetic Resonance image was performed 36 months following operation. There was no radiologic and clinical evidence of regrowth in three-year follow-up.
Conclusions: To date, we report herein 63 cases of accessory nerve schwannomas, which include 62 cases reported from the literature review and a new case reported herein. Only 5 of accessory nerve schwannomas were strictly located at cerebellomedullary cisterna. We present a new case of schwannoma located at cerebellomedullary cisterna. We performed a comprehensive review of accessory nerve schwannoma, describing more cases than those previously reported. This review characterizes a rare disease and increases awareness of this disease among neurologists and otolaryngologists.
- Southern Tohoku General Hospital, Japan
- Title:Diagnosis and Treatment of Co-Existence of Pituitary Adenoma and Rathke's Cleft Cyst. ~Results of a Prospective Study~
- Time :
The frequency of coexistence of pituitary adenoma and RCC was reported to be 1.9%, and it was considered to be very rare, and it was found that Rathke’s cleft cyst (RCC) was complicated with the pituitary adenoma at a high rate, since MET-PET became diagnosable to the pituitary microadenoma. Between 2011 and 2014, we initiated a prospective study with concomitant pituitary adenomas in mind in cases of RCC and examined the frequency of concomitant pituitary adenomas associated with RCC. Based on the results, from 2015, we examined the frequency of precedent RCC lesions in cases with pituitary macroadenomas as a prospective of preoperative diagnosis.
Part1: From 2011 to 2014, 308 surgical cases with prospective analysis for patients with RCCs were included. Male: 77 cases, female: 231 cases. The average age was 39-year-old, ranging from 11-year-old to 82-year-old. Basal pituitary hormones and the presence of abnormal findings in the sellar region on 3D-CT were screened for those with symptoms of headaches and dizziness and suspected RCCs. When abnormalities were observed in the screened items, 3T-MRI features including 3D-Flair cube images and hormonal challenge tests were added. If hormonal loading test showed abnormal ACTH, GH secretions, MET-PET was added and fused images with 3T-MRI were created. Surgical treatment of both complicated lesions was performed at the time of surgery, and pathological examination was performed.
Part2: The complication rate of RCC, which is assumed to be the antecedent lesion of pituitary adenoma, was examined for prospective in macroadenoma operation case under the result of Part1.We studied pituitary tumors in 42 consecutive surgical cases from 2015 to 2016. Scores of headache and detailed preoperative medical history were taken with the combination of RCC and adenoma in mind. Radiological image has been added to sensitive methods for detecting RCCs, namely, 64-channel 3D-CT reconstruction imaging and, more 3T-MRI, conventional imaging, plus flair cube 3D and SPGR techniques. As an intraoperative finding, in cases of suspected ruptured RCC, we check the presence or absence of indirect finding not obtained by histology (presence of fissures within the pituitary gland, ruptured foramen, and venous lake of the dura mater).
Part1: From radiological examination and operative findings, 308 cases of RCC were diagnosed. Among them, pituitary adenomas were histopathologically confirmed in 106 cases, 111 adenomas. Therefore, the rate of concomitant adenoma and RCC was 34%. 100 out of 106 pituitary adenomas showed the diameter less than 10mm (microadenoma). Of the 106 cases, 28 had adenoma confirmed by pathological examination alone, and 78 had adenoma visualized by MET-PET, which was also confirmed by surgical pathological specimens. Breakdowns of adenomas were GH production in 40 cases, ACTH production in 36 cases, PRL production in 14 cases, and others in 5 cases.
Part2: Among 42 consecutive surgical cases, 34 cases were diagnosed as pituitary adenomas. Among those 34 cases of pituitary adenoma, complication of RCC was confirmed in 9 cases, which were pituitary adenoma and suspective preceded lesion.
The complication frequency of macroadenoma and ruptured RCC was 26%. Types of adenomas included PRL production (1 case), Gonadotrpin production (1 case), and GH production (1 case), PRL & GH production (2 cases), TSH production (1 case),
plurihormonal adenoma (2 cases), and Null cell adenoma (1 case). Thus, all types of hormone-producing adenomas were seen.
1, Ruptured RCC has the risk of forming pituitary adenomas, and when diagnosing
and treating RCC, it is important to carry out the retrieval considering also the pituitary
2, Approximately 26% of pituitary macroadenomas were expected to form based on ruptured RCCs.
3, In the medical examination of the pituitary adenoma, the combination of RCC is always kept in mind, and precise hearing, endocrine examination, diagnostic imaging are also important for understanding the disease state in deciding the treatment plan.
Dr. Hidetoshi Ikeda Graduated from Tohoku University School of Medicine in 1981. He learned and had training both Neurosurgery and General pathology at Tohoku University and obtained MD and PhD. He worked as visiting scientist at Dept of Neuropathology, University Hospital, Zurich, Switzerland (1992) and at Dept of Molecular biology, Harvard Medical School, Boston, USA (1993). He accomplished more than 2500 cases of transsphenoidal surgery for pituitary tumors at Tohoku University, Kohnan Hospital, Ohara medical center Hospital and Southern Tohoku General Hospital during the period of 1990~2016. For this great achievement and success he had won many prizes, such as “Joseph Lister Research Awards-2015 in Neurology”, “Archimedes Research Award-2015 in surgery”, “Academic Excellence Award-2015”, “Takahashi memorial award in 2016”, and Albert Nelson Marquis Lifetime Achievement Award in 2017.
- Zhejiang Provincial People’s Hospital, China
- Title:Effect of Hemodynamic Characteristic Changes of the Carotid Artery on 6-OHDA-Induced Parkinson’s Disease Model Rats Treated by Gut-Acupuncture
- Time :
Parkinson’s Disease , is the most common motor relateddisorders up to date. Since
the discovery of levodopa half a century ago, which may cause a ‘‘honeymoon period”as well
as side effects. Recent studies have reported that acupuncture is the most commonly used
complementary and alternative therapy (CAM) for a large number of PD patients besides
standard treatment.In recent years, the development of PD research has been focused on the
gastrointestinal tract and the related ENS. Combining findings from gut-brain axis studies
about early warning gastrointestinal (GI) symptoms in PD and the course of the ‘‘stomach
meridian” in Huangdi Neijing, we employed a 6-OHDA rat model, to elucidate the
mechanisms of acupuncture–mediated amelioration of PD symptoms.Our data show that gut- acupuncture correlates with significantly increased abundance of TH, a marker of DA
neurons compared to untreated rats. Furthermore the area of SNH in the injured side of the
acupuncture group was significantly reduced. PSV of LCCA, LICA,RICA showed that were
significantlyimproved i.e. decreased in the acupuncture group, while the diameter of LICA
and RCCA in acupuncturegroup was narrower. We also found that the PSV was significantly
increased and the vascular diameternarrowed in LCCA and LICA during treatment, whereas
after removing the acupuncture needle the PSVdecreased and the vascular diameter widened. In short,Gut-acupuncture can reduce SNH and influence TH abundance in the SN which
correlatedwith changes of hemodynamic characteristics of the lesioned side. We suggest a
regulatory mechanismwhich may affect the vagus nerve through the ENS and cause the
change of cervical hemodynamics. Itfurther induces low oxygen tension microenvironment
conducive to the proliferation of neural stem cells,which leads to the enrichment of TH in PD
model rats of acupuncture group.
Dr. Li Lihong is an Associate Professor, Master’s tutor,vice-directors.She graduated from
Zhejiang University of traditional Chinese medicine in 2009, and then worked in the
Department of acupuncture and moxibustion of Zhejiang Provincial People’s hospital. She graduated from Zhejiang University of traditional Chinese medicine in 2009, and
then worked in the Department of acupuncture and moxibustion of Zhejiang Provincial
People’s hospital. She has been engaged in acupuncture clinical work for 11 years, and has
been committed to the research on the mechanism of acupuncture and moxibustion on
regulating neuroimmunity. Good at acupuncture treatment of Parkinson’s disease, myasthenia
gravis, depression, anxiety, sleep disorders, tension headache, migraine, facial paralysis and
so on. She has published a textbook of acupuncture and moxibustion, serving as a member of the
sleep Management Committee of the Chinese Acupuncture Association, a member of the
meridian Committee of the acupuncture society, and a member of the pain society of
traditional Chinese medicine.
- Virgen del Rocío University Hospital, Spain
- Title:Antibody-Mediated Encephalitis
- Time :
Antibody-mediated encephalitis is a novel entity in neurology on which there are important advances in pathophysiology, diagnosis and treatment, and is currently considered a rare but with increasing frequency.
Its diagnosis is fundamentally based on antibodies, which are usually delayed, so its early diagnosis is important to reduce sequelae and mortality and requires close monitoring for at least two or three years in search of an associated neoplasm.
Its diagnosis is based on epidemiological, clinical, neuroimaging, fluid, electroencephalographic, nuclear medicine, and the antibodies described, but since they are delayed, we move to the level of certainty “Probable Antibody-Mediated Encephalitis” to start treatment in acute phase and thus reduce sequelae and mortality. It should be noted that these antibodies are not found in half of the patients, which further justifies the follow-up of these patients and the approach to alternative diagnoses.
The purpose of this Oral Communication is to review the most relevant aspects of this entity, focusing on the importance of early diagnosis and the need to have Reference Laboratories to improve efficiency in the detection of antibodies, as well as the need for Increase research items to better understand the pathophysiology of this entity and improve prescribed treatments.
Dr. Francisco Jose is graduated from Medical School in 1991 (Sevilla).He completed his training as neurology resident in Hospital Virgen de las Nieves in Granada (1993-6).He received his Ph. D in 2007 with certificate “Cum Laudem”, in University of Sevilla “ Epidemiology in Multiple Sclerosis in the island of Lanzarote and its variations in the last years”.He received his Master’s Degree in Neuroimmunology from University of Barcelona in 2009.He received his Master’s Degree in Direction of Social-sanitary Servicies from University of Extremadura in 2011.He received the University Expert Degree in Neuropsicology, in Pablo Olavide University, Sevilla in 2010.
Title “Neurologist for the future”, by Spanish Neurological Society. Currently he is the secretary of Andalusian Neurological Society.He is also a Clinic Tutor in pre/post-grade formation.He is a Regular copy editor of the Neurología magazine.
- Ben-Gurion University of the Negev, Israel
- Title:Pyruvate Administration Reducing Lesion Volume, Brain Edema and the Extent of BBB Permeability 24 hours Post-MCAO.
- Time :
Introduction: It is well known that abnormalities elevated glutamate levels in the brain are associated with secondary brain injury following acute and chronic brain insults. As such, a tight regulation of brain glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess glutamate. Pyruvate, via blood resident enzyme glutamate-pyruvate transaminase convert glutamate into its inactive form 2-ketoglutarate. This method of reducing excess glutamate, known as blood glutamate scavenging (BGC). The objective of the present study was to investigate the efficacy decrease in blood glutamate concentrations in the injured brain results in reduced cerebral edema, infarct zone and BBB breakdown.
Methods: Eighty Sprague-Dawley male rats were randomly assigned into one of three groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment (n=30), MCAO plus placebo treatment (n=30), and sham operated rats (n=20). The pyruvate was administrated intravenous after MCAO. Equal volumes of isotonic saline without pyruvate were given to the placebo group. The neurological status, brain infarct zone, brain edema, BBB breakdown (by MRI technique) and blood glutamate levels were also evaluated.
Results: Our results showed that rats after MCAO demonstrated reduced lesion volume, brain edema and the extent of BBB permeability 24 hours post-MCAO . Treatment with pyruvate also led to reduced glutamate levels 24 hours after MCAO and improved neurologic recovery.
Conclusion: Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke.
Academic Education: M.D 2001 – 2007 Shevchenko Moldavian State University Faculty of Medicine; PHD 2018 – presented at Ben Gurion University in Negev, Beer Sheva, Title: “The effect of blood glutamate scavenging by pyruvate on long – term behavioral patterns after acute brain injuries in rats”.
Professional Training: 2007–2009 Therapy Residency, Republican Clinical Hospital, Tiraspol, Moldova; 2012-2017 Anesthesia Residency, Soroka University Medical Center, Beer Sheva, Israel.
Employment History: 2017 – present Attending in Department of Anesthesiology, Soroka University Medical Center, Beer Sheva, Israel. Academic Appointments: 2018-2019 Clinical Instructor, Division of Anesthesiology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel. 2019 – present Lecturer. Division of Anesthesiology and Intensive Care, General Intensive Care Unit, Soroka University Medical Center Faculty of Health Science, Ben Gurion University of the Negev Beer Sheva, Israel. Educational Activities: 2015 – 2016 Pharmacist course, 4 years. Ben Gurion University of the Negev, 2017 – present Medical Student course, 6 years. Ben Gurion University of the Negev, 2018 – present Anesthesiologist resident course. Ben Gurion University of the Negev.
- Newcastle University, UK
- Title:Increased Telomerase Improves Motor Function and Alpha-Synuclein Pathology In A Transgenic Mouse Model Of Parkinson’s Disease Associated with Enhanced Autophagy
- Time :
Protective effects of the telomerase protein TERT have been shown in neurons and brain. We previously demonstrated that TERT protein can
accumulate in mitochondria of Alzheimer’s disease (AD) brains and protect from pathological tau in primary mouse neurons. This prompted us to employ telomerase activators in order to boost telomerase expression in a mouse model of Parkinson’s disease (PD) overexpressing human wild type -synuclein. Our aim was to test whether increased Tert expression levels were able to ameliorate PD symptoms and to activate protein degradation.
We found increased Tert expression in brain for both activators which correlated with a substantial improvement of motor functions such as gait and motor coordination while telomere length in the analysed region was not changed. Interestingly, only one activator (TA-
65) resulted in a decrease of reactive oxygen species from brain mitochondria. Importantly, we demonstrate that total, phosphorylated and aggregated -synuclein were significantly decreased in the hippocampus and neocortex of activator-treated mice corresponding to enhanced markers of autophagy suggesting an improved degradation of toxic alpha- synuclein. We conclude that increased Tert expression caused by telomerase activators is associated with decreased -synuclein protein levels either by activating autophagy or by preventing or delaying degradation mechanisms which are impaired during disease progression. This encouraging preclinical data could be translated into novel therapeutic options for neurodegenerative disorders such as PD.
Dr. Saretzki graduated from Sankt Petersburg (Russia) University 1982 and did her PhD at the Department of Genetics at the Humboldt-University Berlin (Germany) in 1990.
Since 1990 she was involved in ageing research and worked on telomeres, telomerase, oxidative stress, DNA damage and cellular senescence. Since 2001 she worked at Newcastle University (UK) where she became a lecturer in Ageing Research in 2002. In particular, her research interest were functions of telomerase in cancer and stem cells as well as non-canonical functions of the telomerase protein TERT in mitochondria. She extended this work to non-canonical functions of TERT in brain with an interest in neurodegenerative diseases.
- Nara Medical University, Japan
- Title:Hypothalamic Neurons Modulate Behavioral Responses to a Potential Threat.
- Time :
Defensive behaviors are evolutionarily conserved responses to threat stimuli. There are two types of threat stimuli, actual and potential. Actual threats such as predators and intruders elicit fight, flight, and freeze responses. Otherwise, a potential threat such as a novel object evokes risk assessment behavior to correct risk information. Many studies have focused on the neural mechanisms underlying fight-flight-freeze responses, while those of risk assessment are hardly understood. Our recent study revealed that hypothalamic perifornical neurons modulate risk assessment behavior in mice. Perifornical urocortin-3 neurons respond to a novel object stimulus and their neuronal activity is associated with the risk assessment of a novel object. The activation of these neurons enhanced risk assessment and burying behavior. Burying is one of the active forms of defensive behavior and is also known to be a marker for repetitive/stereotypic behavior. The ablation of these neurons caused abnormal behaviors, such as gnawing and direct contact with novel objects. These findings indicate that hypothalamic neurons modulate defensive behaviors in response to a potential threat, which is a new function of the hypothalamus.
Dr. Noriko Horii is a Lecturer of Anatomy and Cell Biology in Nara Medical University from 2016‒Present.
From 2006‒2010 she was an Assistant professor of Anatomy and Cell Biology in Nara Medical University and the Assistant professor of Parasitology in Nara Medical University. In 2006 she received a Ph.D. in Kyoto Institute of Technology, Graduate School of Science and Technology
Her Research focus is: Behavioral neuroscience, the extracellular matrix in the brain
She also earned Awards of: Encouragement Award of the Japanese Association of Anatomist (2015), Young Investigator Award of the Japan Neuroendocrine Society (2013)
- GVK Emergency Management Research Institute, India
- Title:The Role of 108 GVK EMRI Ambulance Services in the Management of Behavioral Emergencies in the State of Telangana
- Time :
Mental health is a major public health issue that calls for immediate steps by individuals and societies around the globe. Talking about mental health issues has always been considered a taboo, especially in lower-middle income countries. This paper assesses the role of GVK Emergency Management Research Institute (GVK EMRI) 108 Ambulance Services in the management of behavioral emergencies in the state of Telangana, India. Primary data collection was carried out in Devaryamjal village of Medchal District with people from both rural and urban setting. The use of management services for behavioral emergencies are described, and knowledge attitude and practices in communities regarding the use of these services are identified. The impact of the Covid-19 pandemic on the mental health of individuals is considered as well, and recommendations to strengthen 108 services for managing behavioral emergencies are suggested. As GVK EMRI is a first responder organization, understanding its role in the field of behavioral emergencies can fundamentally impact several lives. Findings indicate that mental health problems exist in communities, but individuals are reluctant to seek help. People from the urban setting were more open to talk about the topic. The awareness of 108 as an emergency response service was immaculate and a positive view was held about the services and the organization.
Ms. Eshita Raju Kalidindi is an undergraduate student at the University of San Francisco pursuing Psychology and Entrepreneurship & Innovation. She has been involved in various research projects. Her most recent research project focused on the Role of 108 Ambulance Services in the Management of Behavioral Emergencies in the state of Telangana. She identified the knowledge attitudes and practices of members in the community with regards to behavioral emergencies and provided recommendations to improve the services of 108 in India. In the past she has also identified the correlation between social media usage and depression in young adults and her paper is currently in the publication process. At present, she is currently working with Dr. Johnathan Cromwell at the University of San Francisco on identifying how creative thinking and creative problem solving are influenced by positive and negative emotions.
- University of Sao Paulo, Brazil
- Title:Brain-Linguistic Integration for Artificial Intelligence
- Time :
The perception of human language as an integrated process in the brain combines the stimuli collected from the environment with their organization as in a broader context to prepare appropriate responses. This integration is made possible by the universal structure of language, an architecture based on axiomatic (specialized subsystems that collect stimuli) and logic (brain function that aggregates and organizes stimuli). This structure is compared to the use of artificial neural networks, which does not present satisfactory intuitiveness and consistency. In this work, semantics and statistics are applied to semantically evaluable information to contrast the universal consistency of human language and the ideal consistency of AI. It is suggested that the deep learning techniques that guide the algorithms apply the axiomatic-logical principles of the language to overcome interpretability difficulties, making them overlap in the cognitive architecture of biological and intelligent systems. Semantics and statistics placed side by side to show that the ‘key’ to a good information classifier is in the dynamic aspect of the language (process) with access to weights (context values), as it makes the AI invariant to many input transformations and avoids semantic distortion.
Post-doctoral Researcher at the Department of Computation and Mathematics of Faculty of Philosophy, Sciences and Letters of Ribeirao Preto – University of Sao Paulo, FFCLRP-USP, Brazil; Collaborating researcher at Language Institute of University of Campinas, IEL-UNICAMP, Brazil. Faculty Member at Law Department of University of Ribeirao Preto, UNAERP, Brazil. Direct Doctoral degree in Psychology, FFCLRP-USP, Brazil. Doctoral degree program partly completed at Université Paris III, Sorbonne Nouvelle (2010, CAPES-BEX). Internship at École des Hautes Études en Sciences Sociales, EHESS Paris (2012, FAPESP). Undergraduate degrees in Languages and Law. Member of the research center group to advance artificial Intelligence in Brazil, C4AI, Center for Artificial Intelligence, (USP, IBM, FAPESP). Member of the British Wittgenstein Society. Associate Researcher, National Science Network for Education (Rede CpE, Brazil). Review Editor of Frontiers in Mathematical Physics. Member of Editorial Board and Reviewer of International Scientific Journals.
Research interest: Neuroscience; Neurolinguistics; Brain Impairment; Artificial Intelligence; Neurophysiology; Natural Language. Computational Linguistics.
Recent publications: Monte-Serrat, D; Cattani, C. (2021) The natural language for Artificial Intelligence. Elsevier-Academic Press; Monte-Serrat, D. (2021); Monte-Serrat, D. (2021). Operating language value structures in the intelligent systems. Advanced Mathematical Models & Applications, 6(1), 31-44; Monte- Serrat, D. M., & Cattani, C. (2021). Interpretability in neural networks towards universal consistency. International Journal of Cognitive Computing in Engineering, 2, 30-39.
E-mail email@example.com ORCID iD http://orcid.org/0000-0002-4266-8979 ResearcherID URL
– http://www.researcherid.com/rid/D-5222-2017 Curriculum Vitae http://lattes.cnpq.br/1892922460567339
- Catholic University of Brasília, Brazil
- Title:The Physical Education and the Infantile Systemic Hyalinosis: A Case Report
- Time :
The purpose of this case report is to present the case study of a child with Systemic Infantile Hyalinosis in the educational attendance specialized in Physical Education and Art (dance). The collection took place through the Teachers’ Field Diary and the interview with the child’s mother. The pedagogical intervention lasted 15 months and took place at the swimming and dance workshops, with two weekly classes in each workshop lasting 30 min each. The intervention was based on Henri Wallon’s theory of emotions and sought freedom of expression, body experience, and the discovery of a body marked by disease and, in many moments, disrespected in its possibilities. At the end of the intervention, there were no gains in mobility and range of motion in terms of motor, which were compromised due to the instability caused by the progressive disease.There were significant gains regarding self-esteem, which were relevant and significantly contributed to a better quality of life of the child. The rarity of the case makes it difficult to compare the results with the other cases of diseases and disabilities, but the good results obtained allow to open the discussion to other illnesses that are often disregarded by Physical Education due to their severity and complexity in view of the paradigms of the arean, including allowing the replication of the study in other children with disabilities or serious illnesses, based on the use of the founding principles of the proposed pedagogical intervention, provided that individual characteristics and needs are considered.
Graduated, Master and Doctor in Physical Education with specialization in Specialized Educational Service for people with disabilities (Autism, Intellectual Disability and Multiple Disability) and in Psychomotricity. Professor at the State Department of Education of the Federal District and former professor at the Catholic University of Brasília. Author of the books: “Henri Wallon and Multiple Disability – a proposal for pedagogical intervention” and “Proposal for bodily intervention for Autists”.
- Pontificia Universidad Católica, Chile
- Title:Impact of COVID-19 Pandemic on Stroke Severity and Mortality in the South-East of Santiago, Chile
- Time :
Background and purpose: Chile has been one of the most affected countries by the COVID-19 pandemic, with one of the highest case rates per population. This has affected the epidemiological behavior of various pathologies. We analyze the impact of the pandemic on the number of admissions due to stroke, its severity and mortality in Santiago, Chile.
Methods: a multicenter observational study based on the records of the 3 hospitals of the South East health service in Santiago, Chile. We recorded the number of patients admitted for ischemic stroke between 01 January 2020 and 30 June 2020. We grouped the cases into two periods, pre-pandemic and pandemic, according to the setting of the state of emergency in Chile.
Results: 431 patients were admitted with ischemic stroke during the study period. There was a non-significant decrease in weekly admissions (17 vs 15 patients per week). No differences were observed in the proportion of patients with medical treatment (p = 0.810), IVT (p = 0.638), EVT (p = 0.503) or IVT + EVT (p = 0.501). There was a statistically significant increase in the NIHSS on admission (7.23 vs 8.78, p = 0.009) and mortality (5.2% vs 12.4%, p = 0.012). In a multivariate analysis the NIHSS on admission was associated with the increased mortality (RR 1.11, CI 1.04-1.19, p = 0.003).
Conclusion: We found an increase in the severity of ischemic stroke on admission and in-hospital mortality during the pandemic period. The main factor to increase in-hospital mortality was the NIHSS on admission.
Andrés Silva is a Professor of Neurology at Pontificia Universidad Católica (Santiago, Chile). He studied neurology at the Pontificia Universidad Católica de Chile and is a vascular neurologist trained at the Germans Trias i Pujol Hospital (Barcelona, Spain). He is the head of the stroke unit at Sótero del Río Hospital (Santiago, Chile)
- Buck Institute, USA
- Title:Senolytic Intervention in Neurological Diseases
- Time :
Cellular senescence is a potential tumor-suppressive mechanism that generally results in an irreversible cell cycle arrest. Senescent cells accumulate with age and actively secrete soluble factors collectively termed the senescence-associated secretory phenotype (SASP), which has both beneficial and detrimental effects. Although the role of senescent cell contribution to age-related pathologies has been well established outside the brain, emerging evidence indicates that brain cells do undergo cellular senescence and contribute to neuronal loss in age-related neurodegenerative diseases. The significant contribution of the senescent cells in the pathogenesis of neurological disorders has led to the possibility of eliminating senescence cells via pharmacological compounds called senolytics. Recently several senolytics have demonstrated improved cognitive performance and healthspan in mouse models of neurodegeneration, indicating the beneficial effect of selective elimination of senescent cells. However, even though senolytics have proven to improve brain pathology, their translation for use in the clinic holds several potential challenges.
Julie Andersen received her PhD from the Department of Biological Chemistry, UCLA School of Medicine. She conducted her postdoctoral training in the Neurogenetics Unit at Massachusetts General Hospital East in the Department of Neurology at the Harvard Medical School. She joined the School of Gerontology at the University of Southern California in 1992 as Assistant Professor where she held the Paul F. Glenn Chair in Molecular and Cellular Gerontology. She was promoted to Associate Professor at USC in 1999. In 2000, she joined the Buck Institute where she was promoted in 2005 to the position of Full Professor. Dr. Andersen has received numerous awards including a Brookdale National Fellowship, a Glenn Award for Research in Biological Mechanisms in Aging, a Senior Ellison Scholarship, and an Award from the XIX World Congress of Parkinson’s disease (PD). She was elected a fellow of the Society for Free Radical Biology and Medicine in 2013 and received a Parkinson’s Pioneer Award from the National Parkinson’s Foundation in 2015. She serves on several national and international advisory boards and grant reviewing committees and as an editor for several journals in the field.
- Vellore EEG Center, India
- Title:Anterior Thalamic Nucleus Stimulation in Intractable Epilepsy: Optimization of Stimulation Parameters by EEG Based Novel Approach
- Time :
Deep brain stimulation (DBS) of anterior thalamic nucleus (ATN) is establishing as an effective adjunctive therapy for patients with intractable epilepsy (IE) not suitable for epilepsy brain surgery and/or vagal nerve stimulation. The judicious selection of DBS parameters (DBSPs) plays a crucial role in the success of ATN-DBS. Conventionally, DBSPs are selected by trial and error requiring multiple sessions and hospital visits warranting a strong need for optimization of the DBSPs with objective assessment of its effects. The author presents an EEG-guided novel and superior approach to the selection of effective DBSPs targeted to induce EEG-desynchronization, which is known to exert potent antiepileptic influence with possibly possession of an additional anti-kindling effect that can suppress or even arrest the ongoing process of epileptogenesis in the patients with intractable epilepsy in addition to exercising control over the intractable seizures. It is further claimed that the innovative EEG-guided approach can successfully optimize the DBSPs resulting in (a) minimum sessions of DBSP adjustments, thereby reducing the frequency of hospital visits (b) minimum side effects and (c) minimum consumption of the device battery; thus, prolonging its life. Preliminary results of the clinical application of the novel approach in the selection of the DBSPs in a small case series have been very promising and encouraging despite which it is strongly recommended that well designed large sized studies are required for its validation and successful clinical outcome.
Dr. Harinder Jaseja has worked as a faculty member in a Medical school for more than 33 years. His main research interest has been in epilepsy and epileptogenesis; in 2013, he was ranked Second in Epilepsy Research in India.
He has published papers on various aspects of epilepsy, especially association of epilepsy with sleep. He had advocated consideration of diagnosis of epilepsy even after the first epileptic attack (in 2009) long before the ILAE definition of epilepsy in 2014 that permits clinical diagnosis of epilepsy even after one epileptic attack associated with a 60% risk of a recurrent attack. Until this definition, clinicians usually waited for occurrence of a second attack thus delaying the initiation of anti-epileptic medication, causing anxiety and stress in the patients due to uncertainty and unpredictability of a second attack.
His current work has been on Deep brain stimulation (DBS) in intractable epilepsy (IE). He has postulated a new target for DBS, namely Pedunculopontine nucleus (PPN), claiming that its stimulation is superior in therapeutic efficacy and success over the conventional DBS of anterior thalamic nucleus (ATN) in patients with IE.
In 2005, he initiated a debate on the epileptogenic potential of Meditation. He has published new guidelines for treatment of patients with cerebral palsy (CP), based on EEG. He has claimed that CP, contrary to popular belief, can change its course and progression with time and therefore, observation of new guidelines, quality of life of patients with CP may be improved. He has studied the effects of vagal nerve stimulation and has shown and claimed its efficacy in patients with CP, post which, CP has been included in the list of indications of VNS, the links to which are: (http://www.aetna.com/cpb/medical/data/100_199/0191.html,http://www.anthem.com/medicalpolicies/policies/mp_pw_a053286.htm).
He has worked on interpretation of an EEG and shown how its misinterpretation can be prevented; further, he has also ideated how the yield of EEG-findings can be enhanced in patients with epilepsy. He has shown that the hallmarks of epileptiform activity namely ‘spike’ and ‘sharp’ waves (which hitherto were considered having same significance) posses differential clinical significance especially in patients with epilepsy.
Interestingly, he has shown that the Indian traditional application of Shoe-smell in Epilepsy has a sound scientific basis. In a small study, shoe smell was reported to posses beneficial effect (reduction in duration and severity) during an epileptic attack.
- Pasteur Institute, France
- Title:Do Nicotinic Receptors Modulate High-Order Cognitive Processing?
- Time :
Recent studies provided strong evidence that deficits in cholinergic signaling cause disorders of cognition and affect conscious processing. Technical advances that combine molecular approaches, in vivo recordings in awake behaving animals, human brain imaging, and genetics have strengthened our understanding of the roles of nicotinic acetylcholine receptors (nAChRs) in the modulation of cognitive behavior and network dynamics. Here, we review the emergent role of nAChRs in high-order cognitive processes and discuss recent work implicating cholinergic circuits in cognitive control, including conscious processing.
Dr. Jean-Pierre Changeux worked on the bacterial regulatory enzyme, l-threonine deaminase which led to the general discovery that chemical signals that regulate the biological activity of proteins act at “allosteric” sites distinct from the biologically active sites(1961)as a Ph.D. student in Jacques Monod Laboratory, and involved a cooperative conformational transition (Monod-Wyman-Changeux 1965) viewed as a general molecular mechanism of signal transduction. His subsequent career led to the chemical identification of eukaryotic acetylcholine nicotinic receptor, the first identified neurotransmitter/drug membrane receptor and ion channel together with the demonstration of its allosteric properties and of its structural homology with prokaryotic receptors. In addition to the novel concept of allosteric modulators that creates a revolution in the field of drug design, he has brought new perspectives on nicotine addiction, the higher function of the brain and their pathologies.
- Federal Center of Brain Research and Neurotechnologies, Russia
- Title:Optimization of MS Care Organization in Countries of Central and Eastern Europe, Including DMTs Biosimilars and gGenerics
- Time :
Many countries within Central and Eastern Europe are classified as having the highest prevalence of MS. Consistent with the global trend, in the absence of reliable tests or biomarkers, progression at early stage remains undiagnosed. Due to diagnostic uncertainty and lack of a universally accepted disease definition, clinicians rely more on retrospective analysis of the clinical symptoms to confirm the diagnosis. Important problems are the lack of a universally accepted definition for different types of MS, including SPMS, as well as a lack of reliable biomarkers for the condition contribute to diagnostic uncertainty. A poor understanding of the underlying disease mechanisms and difficulty in identifying the early signs of progression make disease management more challenging for clinicians. Frequent follow-up of patients and periodic assessment of progression are recommended for the timely identification of patients transitioning from RRMS to SPMS. Progression is evaluated based on the disability status, as measured mainly by the EDSS, however, assessment of cognitive function is also important for diagnosing and evaluating disease progression, as cognitive impairment heavily influences the lives of MS patients. It is important to perform the cognitive testing from the beginning of the MS course. From a Central and Eastern European perspective, these challenges are further complicated by a longer delay in diagnosis of SPMS and fewer treatment options. Many patients are currently being treated with DMTs not working in progressive course of MS (PPMS and SPMS). The off-label use of DMTs with low effectiveness in patients with delayed diagnosis of SPMS increases the economic burden of MS in these countries. The focus should be on early treatment initiation to delay disease progression. The high cost of DMTS is another important problem in countries of Central and Eastern Europe. This limits the use of several products and decrease the number of patients, who can received DMTs covered by state. One of the possible ways of decreasing cost of MS without losing effectiveness and safety of therapy is the use of biosimilars and generics. In Russian Federation we have a long time positive experience of the use of biosimilars and generics of IFNβ, GA, teriflunomide, DMF and fingolimod, based on the data of clinical comparing studies. The special study studied the attitude of MS patients and MS neurologist to the transfer from original products to biosimilars and generics. The key role of MS specialists if forming the positive attitude and adherence to biosimilars and generics. The future developing of biosimilars and generics without lose of effectiveness and safety of therapy could be one of the important future direction in MS care in Central and Eastern Europe.
Dr. Alexey Boyko gained his MD and PhD from the Russian State Medical University, Moscow and has been Professor of the Department of Neurology and Neurosurgery at this university since 1997. He was the Chief Neurologist of the Department of Health Care of the Government of Moscow in 2001-2015. He works as the Director of the Moscow Multiple Sclerosis Centre and Director of the Institute of Clinical Neurology and Department of Neuroimmunology at the Federal Centre of Brain Research and Neurothechnologies. He was also elected as Honourable Professor of Kazan and Yaroslavl State Medical Universities. He is also a member of the Presidium of the All-Russian Society of Neurologists, Co-ordinator of the Medical Consulting Boards of Moscow and All-Russian MS Societies, President of RUCTRIMS, member of ECTRIMS Council, Member of the Board of the European Charcot Foundation (ECF). In 2017 he was elected as Honored Scientist of Russian Federation. He has published 17 books and more than 900 original publications, he is Co-editor of three medical journals, a member of Editorial Boards of 5 journals, including MSJ and MSRD. The main interest is epidemiology and genetic of MS, neuroimmunology, clinical trials in MS, he is a member of several Advisory Boards of ongoing and finished clinical trials.
- Nara Medical University Hospital, Japan
- Title:Searching for Baby-Friendly Phototherapy to prevent Bilirubin Encephalopathy in Premature Infants
- Time :
Kernicterus (bilirubin encephalopathy), a neurological complication of neonatal hyperbilirubinemia, has been reported, especially in preterm infants, and neonatal hyperbilirubinemia management remains an important issue for neonatal care. Premature infants in severe jaundice often do not have the typical kernicterus symptoms shown, and in infancy, present with hearing loss and athetoid cerebral palsy. Needless to say, phototherapy is a treatment method for neonatal hyperbilirubinemia that has spread worldwide. There is a tendency to think that phototherapy has no adverse events other than effects on the retina. However, according to Morris et al, aggressive phototherapy for extremity very low birth weight infants did not change mortality or the incidence of neurological sequelae. On the contrary, the mortality rate increased for neonates with a birth weight of 500-750 g (Morris BH, et al. N Engl J Med.359, 2008). For this reason, phototherapy is not necessarily a safe treatment. Since 2010, we have conducted clinical studies on neonatal jaundice and animal studies using young rats with jaundice models. As a result, green light has an advantage in reducing photo-oxidative stress response, but blue wavelength is essential to reduce blood bilirubin. (Uchida Y, et al. Early Hum Dev. 91, 2015).This result motivated the pursuit of what would be an effective and harmless treatment to excrete bilirubin more quickly. Under the current management of jaundice, the decision to start or stop treatment is based on blood total bilirubin and unbound bilirubin levels, and bilirubin excretion has not been directly evaluated. In newborns only a few days old, especially preterm infants, liver enzymes and circulation are immature. In addition, bilirubin excreted in the intestinal tract is absorbed into the blood again by the entero-hepatic circulation, so that it is insufficient to evaluate the phototherapy effect used for jaundice treatment only by the blood bilirubin value. That is, the effect of reducing blood bilirubin in a short period of time with phototherapy is presumed to be excreted as a photo-isomer in urine, but currently it can only be detected by a special analysis method such as high-performance liquid chromatography (HPLC). That is, it is difficult to easily measure urinary bilirubin excretion immediately at the bedside. I would also like to mention at this meeting our ongoing work to establish a new method to assess urinary bilirubin excretion using the fluorescent protein UnaG, which binds specifically and strongly to unconjugated bilirubin.
Dr. Yumiko Uchida is a lecturer of division of neonatal intensive care, maternal, fetal and neonatal medical center, Nara Medical University Hospital. She graduated from Nara Medical University in 1995 and majored in Pediatrics at Nara Medical University Hospital. She has been engaged in neonatal intensive care since 1996. She has been studying neonatal hyperbilirubinemia in the last 10 years.
- University of Nebraska, USA
- Title:Neuron Model with Conductance-Resistance Symmetry
- Time :
We will derive a mathematical model for neuron by imposing only a principle of symmetry that two modelers must obtain the same model when one models the conductances of neural channels and the other models the channels’ resistances. Conductance-voltage characteristics for ion transport channels and protein gating channels are both derived. They are expressed as products of maximal conductances and opening probabilities for both types of channel. It gives an explanation to the critical role of spontaneous firing of individual channel pores and to the origin of leak current. The model has a better fit to a classical data than the Hodgkin-Huxley model does. It can also be reduced to a 2-dimensional model qualitatively similar to the FitzHugh-Nagumo equation and be expanded to a model of three ion channels capable of spike bursts. It gives an electrical circuit design for true artificial neuron. The channel opening probability function derived can also be used in the area of AI.
Dr. Bo Deng is a mathematician working in the field of Mathematical Biology. He obtained his PhD from Michigan State University in US. He has been a professor in the Department of Mathematics, University of Nebraska – Lincoln, US, since 1988. He has done researches in a few areas of Mathematical Biology, including Evolutionary Genetics, Population Genetics, Bioinformatics, Neurosciences, Evolutionary Ecology, and Community Ecology. He has also published works in the areas of Dynamical Systems, Bifurcation Theory, and Chaos Theory.
- Neuro-Horizon Pharma, USA
- Title:Drug Development for the Treatment of Amyotrophic Lateral Sclerosis
- Time :
We have previously identified the interaction between mammalian V-ATPase a2-subunit isoform and cytohesin-2 (CTH2) and studied molecular details of binding between these proteins. In particular, we found that six peptides derived from the N-terminal cytosolic domain of a2-subunit (a2N1–402) are involved in the interaction with CTH2 . However, the actual 3D binding interface was not determined in that study due to the lack of high-resolution structural information about a-subunits of V-ATPase. Here, using a combination of homology modeling and NMR analysis, we generated the structural model of complete a2N1–402 and uncovered the CTH2-binding interface. First, using the crystal structure of the bacterial M. rubber Icyt-subunit of A-ATPase as a template , we built a homology model of mammalian a2N1–352 fragment. Next, we combined it with the determined NMR structures of peptides a2N368–395 and a2N386–402 of the C-terminal section of a2N1–402. The complete molecular model of a2N1–402 revealed that six CTH2 interacting peptides are clustered in the distal and proximal lobe sub-domains of a2N1–402, showing that a2-subunit of V-ATPase interacts with two molecules of CTH2. Indeed, using Sec7/Arf-GEF activity assay we experimentally confirmed our model. These data are critical for drug development using: i) in silico computer-aided drug design (CADD) and ii) TR-FRET based high throughput screening (HTS) of the libraries of BBB-permeable small molecules [3,4]. In particular, it was shown that CTH2 interacts with mutant superoxide dismutase 1 (SOD1), a known cause of familial amyotrophic lateral sclerosis (ALS) . Inhibition of CTH2 activity by small molecules protects against ER stress, enhances autophagic flux and reduces the burden of misfolded SOD1. These data indicate that targeting of cytohesins by peptides and/or small molecules in motor neurons may be beneficial for the treatment of ALS.
- The Johns Hopkins University, USA
- Title: Imaging Neurovascular Abnormalities in Neurodegenerative Diseases
- Time :
Energy metabolism is crucial for maintenance of normal brain functions. As the supply of adequate oxygen and energy substrates for local metabolic demands is controlled by blood vessels in the brain, neurovascular abnormalities
may contribute to the neuropathology and functional deficits in brain diseases. Here, I will discuss our work on the investigation of microvascular and metabolic abnormalities in neurodegenerative diseases measured by advanced
MRI technologies developed at ultra-high magnetic field.
Dr. Hua is an Associate Professor in the F.M. Kirby Research Center for Functional Brain Imaging at Kennedy
Krieger Institute, and the Russell H. Morgan Department of Radiology at Johns Hopkins University. Dr. Hua’s research has centered on the development of novel MRI technologies for in vivo functional and physiological imaging in the brain, and the application of such methods for studies in healthy and diseased brains. These include the development of human and animal MRI methods to measure functional brain activities, cerebral perfusion and oxygen metabolism at high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is particularly
interested in novel MRI approaches to image small blood and lymphatic vessels in the brain. Collaborating with clinical investigators, these techniques have been applied 1) to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntingdon’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease (AD) and mental disorders such as schizophrenia; and 2) to map brain functions
and cerebrovascular reactivity for presurgical planning in patients with vascular malformations, brain tumors and epilepsy.
- University of California, USA
- Title:Integrated Stress Response Inhibitor Reverses Sex-Dependent Behavioral and Cell-Specific Deficits After Mild Repetitive Head Trauma
- Time :
Mild repetitive traumatic brain injury (rTBI) induces chronic behavioral and cognitive alterations and increases the risk for dementia. Currently there are no therapeutic strategies to prevent or mitigate chronic deficits associated with rTBI. We previously developed an animal model of rTBI that recapitulates some of the cognitive and behavioral deficits observed in humans. Here we report that rTBI results in an increase in risk-taking behavior in male but not female mice. This behavioral phenotype is associated with cell-specific synaptic alterations in the type A subtype of layer V pyramidal neurons in the medial prefrontal cortex (mPFC). Strikingly, by briefly treating animals’ weeks after injuries with ISRIB, a selective inhibitor of the integrated stress response (ISR), we permanently reverse the increased risk-taking behavioral phenotype and restore cell-specific synaptic function in the affected mice. Our results indicate that targeting the ISR even at late time points after injury can permanently reverse behavioral changes. As such, pharmacological inhibition of the ISR emerges as a promising avenue to combat rTBI-induced behavioral dysfunction.
Dr. Susanna Rosi is a Professor in the Departments of Physical Therapy Rehabilitation Science and Neurological Surgery and the Director of Neurocognitive Research in the Brain and Spinal Injury Center. She is a member of the UCSF Weill Institute for Neurosciences, Kavli Institute for Fundamental Neuroscience, Hellen Diller Cancer Center, Neuroscience Graduate Program, Biomedical Science Graduate Program. Originally from Tuscany, She earned her undergraduate degree and PhD in Biology from the University of Florence, Italy. She trained in the Neural System Memory and Aging center at the University of Arizona before becoming a Faculty Member of UCSF. Her research is focused on understanding the mechanisms responsible for the cognitive dysfunctions observed after brain injury. Her final goal is to identify diagnostic tools for treatment and prevention. She demonstrated the key role that neuroinflammation plays in the development of cognitive deficits. Most notably, she identified therapeutic strategies able to both prevent and restore lost cognition. She received the Bridging the Gap Award from the California Institute for Quantitative Biosciences, the Innovation Award from the Weill Institute for Neurosciences. She serves as PI on NIH (NIA, NINDS and NCI) funded grants, a NASA grant and she also serves as a standing member of the Molecular Neurogenetic study section at the National Institutes of Health and Associate Editor for the Journal of Neuroinflammation.
- University of Illinois at Chicago, USA
- Title:Predicting Autism Spectrum Disorder Using Domain-Adaptive Cross-Site Evaluation
- Time :
The advances in neuroimaging methods reveal that resting-state functional fMRI (rs-fMRI) connectivity measures can be potential diagnostic biomarkers for autism spectrum disorder (ASD). Recent data sharing projects help us replicating the robustness of these biomarkers in different acquisition conditions or preprocessing steps across larger numbers of individuals or
sites. It is necessary to validate the previous results by using data from multiple sites by diminishing the site variations. We investigated partial least square regression (PLS), a domain adaptive method to adjust the effects of multicenter acquisition. A sparse Multivariate Pattern Analysis (MVVPA) framework in a leave one site out cross validation (LOSOCV) setting has been proposed to discriminate ASD from healthy controls using data from six sites in the Autism Brain Imaging Data Exchange (ABIDE). Our results showed that two or more informative connections are Dorsolateral Prefrontal Cortex, Somatosensory Association Cortex, Primary Auditory Cortex, Inferior Temporal Gyrus and Temporopolar area. These interrupted regions are involved in executive function, speech, visual perception, sense and language which are associated with ASD. Our findings may support early clinical diagnosis or risk determination by identifying neurobiological markers to distinguish between ASD and healthy controls.
Dr. Bhaumik is a research assistant professor at Biostatistical Research Center, in the Department of Psychiatry. Her research focuses on Longitudinal Data Analysis, Multivariate Statistical analysis, Graph Theory and applications of Machine Learning Algorithms to Neuroscience and other fields.
- Cairo University, Egypt
- Title:Renin Angiotensin System Activation in Diabetes Induced Cognitive Impairment
- Time :
There is a great concern in learning and memory deficits that develop over time in patients with poorly controlled diabetes. Hyperactivity of the renin- angiotensin system (RAS) is directly associated with β-cell dysfunction and diabetic complications, including cognitive impairment. There is correlation between RAS components found in areas of the brain and cognition, behavior and locomotion. RAS modifiers; aliskiren and captopril protective and molecular effects were investigated on cognitive deficits in the rat hippocampus, a key brain region responsible for memory and cognition. Poorly controlled STZ-diabetic rats were injected subcutaneously with ineffective daily doses of insulin for 4 weeks. The hyperglycemia and pancreatic atrophy caused memory disturbances that were identifiable in behavioral tests, hippocampal neurodegeneration,and the following significant changes in the hippocampus, increases in the inflammatory marker interleukin 1β, cholinesterase, the oxidative stress marker malondialdehyde and protein expression of phosphorylated extracellular-signal-regulated kinase and glycogen synthase kinase-3 beta versus decrease in the antioxidant reduced glutathione and protein expression of phosphorylated glycogen synthase kinase-3 beta. Blocking RAS with either drug along with insulin restored all previously mentioned parameters to normal. Aliskiren stabilized the blood glucose level and restored normal pancreatic integrity and hippocampal MDA level. Aliskiren showed superior protection against the hippocampal degeneration displayed in the earlier behavioral modification in the passive avoidance test and aliskiren group outperformed the control group in the novel object recognition test. We, therefore, conclude that aliskiren and captopril reversed the diabetic state and cognitive deficits through the renin inhibitory effect and blockade of
RAS. Captopril protective effect is related to a reduction in Ang II synthesis. At last, dwindling RAS activity reduce oxidative stress, inflammation state, and modulating protein expression.
Dr. Madonna Magdy Youssef, MSc, received her pharmacy degree from Ain Shams University and master’s degree in the field of pharmacology at faculty of pharmacy, Cairo University in 2019. Currently she is employed as quality assurance specialist in Egyptian Drug Authorization (EDA), she granted a quality management diploma in 2020. The Ph.D. research work is in progress in fruitful collaboration with the National Research Center and the Academy of Scientific Research. The study related to neurocognitive protection from Alzheimer’s disease for healthy aging as well as investigation of possible enhancement of insulin release and sensitivity for diabetic patients. She serves as a reviewer for Elsevier international journal “Pharmacology and Therapeutics”. Her Research interests are overly concerned with critical pathways and applicable drugs related to neurological and cognitive disorders, diabetes as well as immunological diseases.
- Maastricht University Medical Center, The Netherlands
- Title:Subclinical Myasthenia Gravis in Thymomas
- Time :
Background A proportion of thymoma-patients without a history of myasthenia gravis (MG) before thymectomy, appears to have positive anti-AChR-antibodies in the serum. These subclinical MG-patients could be underdiagnosed because analyzation of anti-AChR-antibodies in thymomas is not always performed in patients who did not experience neurological symptoms. The prevalence and long-term outcomes of subclinical MG are never described in literature yet.
Methods: We retrospectively analyzed 398 consecutive patients who underwent a robotic-assisted thoracoscopic surgery at the Maastricht University Medical Center+ (MUMC+) between April 2004 and December 2018. In the MUMC+, a robotic approach is the standard surgical approach in patients with thymic diseases. Inclusion criteria were thymomas, thymectomy performed in the MUMC+ with a follow-up of at least one year and age above 18 years old. Exclusion criteria were patients with thymic carcinomas, refused participation, or those who were lost to follow-up.
Of the 102 included thymoma-patients, 87 patients (85%) were tested for anti-AChR-antibodies before thymectomy, of which 57 patients were diagnosed with clinical MG and seven subclinical MG-patients were found. Of the 15 patients who were not tested for anti-AChR-antibodies, four more subclinical MG-patients were discovered in the years after thymectomy. The median follow-up time was 62 months. In total, 11 subclinical MG-patients were found, with a mean age of 54 years and predominantly females (64%). Ten subclinical MG-patients (91%) developed clinical-MG, within six years after thymectomy. Immunosuppressive drugs were prescribed in five patients. Four patients were diagnosed with a recurrence of the thymoma. No surgical mortality was reported. Two patients died due to a myasthenic crisis.
The prevalence of subclinical MG in thymomas was found to be 10.8%. One in four patients who experienced no neurological symptoms before thymectomy, appeared to have anti-AChR-antibodies and 91% of these patients developed clinical MG within six years after the thymectomy. Analyzing anti-AChR-antibodies in the serum is recommended in all suspected thymomas before a thymectomy is performed.
Key words: thymomas, thymectomy, myasthenia gravis, anti-acetylcholinereceptor-antibodies
Dr. Florit Marcuse is a resident in Pulmonology and PhD Candidate in the Departments of Pulmonology of the Maastricht University Medical Center+ (MUMC+) and School for Mental Health and Neuroscience (MheNS) of the University of Maastricht. In the Netherlands, the MUMC+ is the main center of expertise for the treatment of patients with thymic disorders. Dr. Marcuse has special interest in thymic oncology and associated thymic diseases in myasthenia gravis. Her research focuses on patients who underwent a robotic thymectomy, which is a standard treatment for patients with a thymoma and in most of the patients with myasthenia gravis. The thymic team of the MUMC+ is internationally known for participation in (inter)national research and collaborations.
- Manmohan Memorial Eastern Regional Community Hospital, Birtamode, Nepal
- Title:Pathway to Care in Patients having Mental Illness in Eastern Nepal
- Time :
Background: Patients with mental illness are treated at various levels before receiving specialist treatment. In doing so, the duration of illness is prolonged, treatments received are sub-optimal, and productivity lessened impacting overall outcome. This study aimed to elaborate on the various pathways of care that a mentally ill patient has to go through and its association with socio-demographic profiles. Methods: A cross-sectional study was carried out among patients presenting to Neuropsychiatric outpatient department who along with their caregivers were interviewed using semi-structured proforma and WHO Pathway Interview Schedule. Results: Of the total participants attending the outpatient clinic, 30% were either first attended by a local practitioner or hospital doctor. The duration of illness in 40% was less than a month whereas in 1/3rd of the patients was more than 12 months before presenting to the first treatment. Similarly, 38.8% had treatment latency of at least 31 months duration before receiving specialist treatment.
Conclusion: Majority of patients with mental illness approached health-professionals at first with majority being prescribed psychotropics. Time to approach for first help seeking was better but approach to psychiatric care was delayed. There is a need for improving mental health awareness at different levels to motivate early help-seeking and proper treatment.
Keywords: Mental illness, patients, specialist, treatment
Dr. Sandarba Adhikari, had received Masters Degree in Psychiatry from Institute Of Medicine, Tribhuvan University, Kathmandu, Nepal. He had worked as a Lecturer in Department of Neuropsychiatry, B&C Medical college Teaching Hospital and Research Centre, Birtamode, Province 1 (April 2018- September 2020) and thereafter currently started Psychiatry services in Regional Community Hospital. His professional interests focus on addiction psychiatry, community Psychiatry and Researches. He is fluent in Nepali, English and Hindi. He has done his thesis on “Disulfiram and Naltrexone for Relapse Prevention in Cases of Alcohol Dependence Syndrome” (MD Psychiatry 2017) and few publications in national and international journals. He is also selected as Trainer in WHO E-mhGAP project (Emilia). He is a lifetime member at Psychiatrists’ Association of Nepal (PAN).
- Antwerp University Hospital, Belgium
- Title:The Clinical and Genetic Spectrum in Infants with (an) Unprovoked Cluster(s) of Focal Seizures
- Time :
Self-limited (familial) infantile epilepsy (S(F)IE), formerly known as benign (familial) infantile convulsions (B(F)IC), is an infantile cluster epilepsy with in rule a complete recovery. It is one of common self-limited epilepsy syndromes affecting children. This large group includes benign syndromes like epilepsy with centrotemporal spikes (‘rolandic epilepsy’), Panayiotopoulos syndrome, and the occipital epilepsies (Gastaut and photosensitive types). Landau-Kleffner is a not always benign form.
In self-limited epilepsy syndromes, there is evidence there is both a role for oligogenic and polygenic component in self-limited focal epilepsies. Recently, in 20 out of 57 patients rare candidate variants were identified with typical or atypical self-limited focal epilepsies in childhood.
We analysed a cohort of 23 patients from 21 families, all with an initial diagnosis of self-limited infantile epilepsy. In 12 individuals a pathogenic variation in PRRT2 gene or complete deletion was identified. Pathogenic variants in PCDH19 and KCNQ2 were found in respectively 3 and 1 individuals. One individual had a non-pathogenic variant in ATP1A3 and in 6 others no variants were identified. Most had only one cluster of seizures. We conclude that most children with unprovoked clusters of focal seizures carry a PRRT2 mutation. When clusters reoccur frequently, when seizures are more therapy-resistant and when seizures persist beyond the age of 2 years, another diagnosis or causative gene (than PRRT2) is likely.
- Cedars-Sinai Medical Center, Canada
- Title:Identification and Management of Cerebrospinal Fluid Leak after Lumbar Total Disc Replacement
- Time :
Lumbar total disc replacement (TDR) is an increasingly common intervention for discogenic back pain, particularly in the younger patient where motion preservation is paramount. This procedure however is not without complications. A CSF leak after lumbar TDR is rare; as such there is a paucity of literature regarding the operative approach to this uncommon pathology. Identification of the CSF leak is the primary step toward successful repair. Multiple modalities may be required such as MRI, CT myelogram, or digital subtraction myelogram (DSM). Successful CSF leak after lumbar TDR may range from simple procedures such as epidural blood patching or lumbar drain, while more significant dural injuries may require repeat operative intervention. Repeat surgery may involve transdural repair or additional measures such as replacement with an alternative implant and primary repair of the leak.
Dr. Julie L. Chan is currently a Neurosurgery Resident at Cedar-Sinai Medical Center. She received her B.S. in Neurobiology from the University of California, Irvine and her M.D.-Ph.D. in Neuroscience from the Medical College of Virginia. Her clinical and research interests include spinal deformity and spine outcomes.
- SUNY Downstate Health Sciences University, USA
- Title:Early Levetiracetam Treatment Prevents the Development of Evoked and Spontaneous Epileptiform Discharges In In Vitro and an In Vivo Model of Cortical Neurotrauma: Clinical Implications
- Time :
Traumatic brain injury (TBI) is a major public health problem and a significant cause of epilepsy worldwide. Effective interventions to prevent post-traumatic epilepsy have proved elusive, in part because TBI is a complex and heterogeneous condition. Our research group has studied 2 rat models of TBI associated epileptogenesis, the in vitro traumatized slice and the in vivo controlled cortical impact (CCI) model. This presentation will describe our recent investigations into the antiepileptogenic efficacy of the pyrrolidine antiseizure drug, levetiracetam (LEV) may prevent epileptogenesis after TBI.
In vitro studies were conducted on traumatized slices of rat neocortex (P21-32) that were prepared using published methods. Randomly selected traumatized slices were treated with clinically correlated concentrations of LEV added to the bath for 1 hour starting immediately after the injury or after a delay of up to 80 min. Treated and untreated slices were examined for epileptiform activity using intra- and extracellular recordings. For the in vivo model, rats (P24-32) were subjected to non-penetrating focal CCI using published methods. Immediately after injury the injured rats were then given a single dose of either LEV or the saline vehicle intraperitoneally. Ex vivo neocortical slices were prepared 2-3 weeks after CCI and examined for epileptiform activity. The results from the in vitro traumatized slice experiments showed that LEV treatment within 60 minutes of injury significantly reduced the proportion of slices that exhibited stimulus-evoked epileptiform activity by more than 50%. LEV treatment also increased the stimulus intensity required to trigger epileptiform bursts by 2-4 fold. Consistent with these findings, in vivo LEV treatment of CCI-injured rats significantly reduced the percentage of animals that exhibited spontaneous and stimulus-evoked epileptiform bursts compared to saline-treated controls. In addition, LEV also significantly increased the stimulus intensity required to evoke epileptiform bursts in slices prepared from CCI-treated animals. These results suggest that early administration of LEV has the potential to prevent or reduce posttraumatic epileptogenesis and highlights that there may be a narrow time window for successful therapeutic intervention. The challenges of using animal models for human epileptogenesis, the clinical implications and limitations of these two models of posttraumatic epileptogenesis, and potential strategies to address prevention or mitigation of post-traumatic epilepsy will be discussed.
Dr. Helen A. Valsamis is a Professor of Clinical Neurology at SUNY Downstate Health Sciences University and the Chief of the Neurology Service at H+H Kings County Hospital. As a clinician-scientist she travels between the clinical and research worlds, now often by virtual means. For the past 15 years she had served as the Chief of the Neurology Service in the second largest public hospital in the United States. She had also been a Residency Program Director for Adult Neurology and an educator of residents, fellows, medical students, attending physicians, nurses, nurse practitioners, EEG technicians, EMTs, patients, and patients’ families. At Kings County Hospital they have a developing neuroscience center which, in partnership with SUNY Downstate Health Sciences University includes a neuroscience research program they have participated in the NETT, SIREN, and Neuro NeXT networks.
- Indiana University Health, USA
- Title:Compounding Nimodipine Oral Suspension for Subarachnoid Hemorrhage
- Time :
What happens when there is an entire patient population, not just a specific patient, which cannot take a commercial pharmaceutical product due to significant adverse effects, although the commercial product has a U.S. Food and Drug Administration-approved indication for the medical problem? What should or can be done in this situation? This presentation discusses this dilemma using subarachnoid hemorrhage as an example of a true documented medical need, and discuss the option and circumstances surrounding the compounding of a nimodipine oral suspension, a U.S. Food and Drug Administration-approved indication for the treatment of subarachnoid hemorrhage.
The learning objectives include the following:
• Discuss the need for an oral nimodipine liquid.
• Provide options for treating patients with subarachnoid hemorrhage.
• Provide information on compounding nimodipine oral suspension to avoid adverse effects.
Dr. McElhiney is the Team Lead Compounding Pharmacist and a preceptor for Indiana University Health in Indianapolis, Indiana. It is one of the largest health-systems in the United States, consisting of 20 hospitals and dozens of outpatient clinics and surgery centers.
She is an author for the International Journal of Pharmaceutical Compounding and contributing author in pharmacy and medical textbooks. Dr. McElhiney is a full fellow in the American College of Apothecaries (ACA), American Society of Health-System Pharmacists (ASHP), and the International Academy of Compounding Pharmacists (IACP). She has served on several national committees and board of directors in professional pharmacy organizations and received several awards. Dr. McElhiney currently serves as the President-Elect for the American College of Apothecaries.
Dr. McElhiney earned a B.S. in Pharmacy from Purdue University in 1984. Dr. McElhiney earned a Pharm.D. (2002) and a Masters (2012) from the University of Florida.
- Bloodworks Northwest, USA
- Title:Traumatic Brain Injury-Induced Coagulopathy
- Time :
Uncontrolled hemorrhage accounts for 30–50% of all trauma fatalities and is caused by direct injury to the vasculature and by secondary coagulopathy. Common causes of coagulopathy after severe trauma to the body and limbs include significant blood loss (hemorrhagic shock), hemodilution and hypothermia due to fluid resuscitation, systemic metabolic acidosis due to tissue ischemia, dysfunctional platelets and coagulation, and hyperfibrinolysis. However, coagulopathy is also common in patients with severe traumatic brain injury, even though these patients lack the key causal factors for trauma-induced coagulopathy. Traumatic brain injury-induced coagulopathy (TBI-IC) is a bleeding diathesis that result in secondary, delayed, or recurrent intracranial or intracerebral hemorrhage. It is mechanistically distinct from deficient and dilutional coagulopathy arising after extracranial trauma and hemorrhagic shock. Extensive clinical and laboratory findings suggest that TBI-IC is consumptive in nature and is developed through a rapid transition from a trauma-induced hypercoagulable state to a hypocoagulable state. Brain-derived extracellular vesicles (BDEVs) have been identified as a key disseminating and causal factor for TBI-IC because these BDEVs express multiple procoagulant factors such as tissue factor and abundant anionic phospholipids such as phosphatidylserine. Upon release into the circulation, these BDEVs serve as circulating platforms on which extrinsic coagulation is initiated and propagated, thus consuming the coagulation factors.
Dr. Jing-fei Dong, MD, PhD is a member of the Bloodwork Research Institute and a professor of medicine in the Division of Hematology, Department of Medicine, the University of Washington School of Medicine. His research focuses on bleeding and thrombotic complications of traumatic brain injury. He is particularly interested in studying the pathways through which TBI induces a systemic hypercoagulable state and resultant coagulopathy. He also studies the structure-functional correlations of the adhesive ligand von Willebrand factor and its cleaving metalloprotease ADAMTS-13 for regulating hemostasis, which is a physiological process of preventing bleeding, and thrombosis, which develops when the hemostatic process becomes aberrant or excessive.
- Dankook University College of Medicine, Kore
- Title:Endovascular Treatment with Stents in Ruptured Complex Aneurysms
- Time :
Stent using in intracranial aneurysms has been avoided by most operators because of concerns about the risk of using dual antiplatelet therapy in the setting of acute SAH.
In case of posterior communicating artery aneurysm with fetal type artery incorporated on aneurysm or broad necked appearance, it was regarded as very difficult to treat endovascularly. However with intracranial stenting maneuver introducing recently, it can be treated completely by retrograde navigation of stent through anterior communicating artery and further coiling with staged approach.
And flow diverters also play important role to treat aneurysms.
The author introduces several technical extensions to overcome the pitfalls in treating the intracranial
Dr. Young Joon Kim is a Korean neurosurgeon, educator. His achievements include research in endovascular aneurysm coiling with stent & endovascular care of acute stroke. He is a member of Korean Society Neurosurgery (board directors since 1998) and he is also a member of Korean Society Intravascular Neurosurgery (president 2002-2004).
- Inra Research Centre, France
- Title:Stunning and Slaughter Techniques: Neurological Mechanisms and Indicators of Consciousness and Unconsciousness
- Time :
At slaughter, animals are generally stunned before bleeding, but society and field workers sometimes question efficacy. Recently, work was undertaken to understand better the neurobiological mechanisms involved in the stunning and killing process of animals. The mechanisms underlying the loss of consciousness depend on the technique used: mechanical, electrical or gas stunning. Direct exsanguination without prior stun, for religious slaughter, causes also a loss of consciousness, before inducing death. Stunning techniques use stun guns, electrified devices or gas mixtures. The principles of stunning and bleeding involve mechanical shock waves and the mechanical destruction of neurons, electrical fields, the reduction or arrest of cerebral blood circulation, or high and/or low levels of CO2 and/or O2, respectively, in inspired air. Effects involve cerebral anoxia or ischemia, the depolarisation, acidification and/or the destruction of brain neurons. Targeted brain structures are the reticular formation, the ascending reticular activating system or thalamus, or the cerebral hemispheres in a general manner. Some of the techniques induce an immediate loss of consciousness, other techniques a progressive loss of consciousness.
To ensure that the animal is unconscious, before further processing, indicators of consciousness and of unconsciousness are verified. They evaluate different aspects of cerebral functioning. As they are imprecise, it necessary to monitor several. As animals may regain consciousness, they are observed until the end of bleeding. Animals are considered unconscious if signs of consciousness are absent, and signs of unconsciousness are present.
Examples of indicators of unconsciousness are the absence of standing posture and of righting movements, the absence of a corneal reflex and respiratory arrest. Indicators of consciousness are the standing posture, coordinated righting movements, specifies-specific vocalizations and a response to the threat test. Often various movements are observed following the stun and during bleeding, including eye tracking, eyeball rotation, nystagmus, head and neck movements and leg paddling. Their presence often leads to confusion on the field as they may be reflex movements, but sometimes they indicate consciousness. Their interpretation needs further discussion.
The techniques used to diagnose brain death in humans cannot be used in the slaughterhouse. Under field conditions, at the end of bleeding, the absence of breathing and of brainstem reflexes and the adequacy of the exsanguination are verified. If these three aspects are confirmed, in the context of the slaughterhouse and at this stage of the slaughter process, the loss of vital functions is irreversible and the animal considered dead.
- Ariel University, Israel
- Title:Intensity-Dependent Effects of Exercise Training in Experimental Multiple Sclerosis
- Time :
Background: Exercise training (ET) has beneficial effects in Multiple Sclerosis (MS)patients and in experimental autoimmuneencephalomyelitis (EAE), the animal model of MS. However, the intensity-dependent effects of ET on the systemic immune system and/or the central nervous system (CNS) remain undefined.
Purpose: To compare the systemic immune-modulatory- and direct neuroprotectiveeffects of moderate vs. high intensity ET protocols on EAE development.
Methods: Healthy mice performed moderate- or high-intensity treadmill runningprograms. Proteolipid protein (PLP)-induced transfer EAE was utilized to enable differentiation between effects of ET on systemic autoimmunity vs. direct effects on the CNS. To investigate the immune-modulatory effects of ET, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. EAE severity in recipient mice was assessed by clinical assessment and histopathological analysis. LN-T cells derived from donor trained vs. sedentary PLP-immunized mice were analyzed in vitro for proliferation by flow cytometry analysis, and for cytokine and chemokine receptor gene expression using real-time PCR. To investigate the neuroprotective effects of ET, PLP-reactive, encephalitogenic T cells were transferred into recipient mice that underwent the training program prior to EAE transfer, and disease severity was compared to that in recipient sedentary mice.
Results: High-intensity training in healthy donor mice induced significantly greater inhibition than moderate-intensity training on proliferation and generation of encephalitogenic T-cells in response to PLP-immunization, and on EAE severity upon their transfer into recipient mice. Additionally, whereas moderate intensity ET did not have direct neuroprotective effects, transfer of PLP-reactive, encephalitogenic LN-T cells resulted in less severe EAE in recipient mice that were subjected to high intensity training program prior to EAE transfer.
Conclusions: Our data, obtained by using a unique experimental design, indicate superior effects of high intensity training on both systemic immune-modulation and direct neuroprotection to inhibit autoimmunity in EAE. This study is of clinical significance and may provide a basis for defining exercise recommendations (that are currently lacking) for MS patients.
Dr.Ofira Einstein graduated physical therapy school in 1999 (B.P.T.) and she completed her doctorate studies in neurobiology in 2006 (Ph.D.). She joined as a faculty of the Physical Therapy department at Ariel University in 2009 and served as the head of the department in years 2011-2017. Prof. Einstein’s research areas are neuro-immunology and neuroregeneration. Her first studies concerned on the neurobiology of neural stem cells and cell therapy, specifically on animal models of human Multiple Sclerosis (MS). Her work published in 2003 was the first to show that transplanted neural stem cells have anti-inflammatory effects on the rodent brain. This finding was a breakthrough for further research of her group, as well as other research groups around the world. Her current research focuses on neuro-immunological, neuro-protective and neuroregenerative effects of exercise training on neuro-inflammatory and neuro-degenerative diseases. These studies are particularly carried on experimental autoimmune encephalomyelitis (EAE), the animal model of her studies involve animal physical training, clinical evaluations, histopathological analyses, cell cultures and molecular biology techniques.
- Ozel Bağlar Hospital, Turkey
- Title:COVID-19: Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome
- Time :
This study presents two new concepts and definitions to the medical literature. One of those is “endogenous retinoic acid theory” and the other “retinoic acid depletion syndrome”. A new classification will be provided for the immune system. “retinoic acid-dependent component” and “retinoic acid non-dependent component”. If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome P450 monooxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called “Endogenous Retinoic Acid Theory”. Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type- I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type-I IFN synthesis stops, and the congenital immune system collapses. Simultaneously, the immune mechanism crosses the TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called “retinoic acid depletion syndrome”. COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is impaired in autoimmune and other chronic inflammatory diseases, and therefore the RIG-I pathway and UPS degradation system are not working properly. Endogenous retinoic acid metabolism is defective in COVID-19 (cytokine storm), sepsis, SIRS, ARDS, severe viral and bacterial infectious diseases, chronic autoimmune diseases and degenerative neurological diseases. This pathogenesis explanation brings a new perspective and treatment approach to this type of disease.
- Queensland University of Technology, Australia
- Title:Antroquinonol Administration in Preclinical Studies for Alzheimer's Disease: A New Avenue for Modifying Progression of AD Pathophysiology
- Time :
Despite the rise of Alzheimer’s disease (AD) in an ageing population, no cure is currently available
for this disorder. This study assessed the role of a natural compound, Antroquinonol extracted from a
Taiwanese mushroom, in modifying the progression of AD when administered at the start and/or before
appearance of symptoms and when the disease was well established, in a transgenic animal model. Male
transgenic mice (3 times Transgenic mice PS1M146V, APPSwe, and tauP301L, 3 Tg XAD) were chosen for this
study due to amyloid beta and tau pathways involved in AD pathophysiology.
Different doses of antroquinonol (7, 34 and 75 mg/kg) were administered daily by oral gavage for
8 weeks, in 11 week- (early stage) and 9 month- (late stage) old male transgenic mice (3 times Transgenic
mice PS1M146V, APPSwe, and tauP301L, 3 Tg XAD) and their respective aged controls. Behavioural testing
(including Elevated Plus Maze Watermaze, Recognition object testing and Y maze) was performed at the
end of the drug administration. Alzheimer’s disease’ biomarkers (amyloid beta 42 (Aβ42), tau and phosphotau levels), oxidative stress and inflammatory markers, were assessed in mouse brains at the end of the
When administered 11 weeks before the start of AD related symptoms at, antroquinonol treatment
at 34 mg/kg (D2) and more consistently at 75 mg/kg (D3), had a significant effect on reducing systemic
inflammatory markers (Interleukin 1, IL-1β and TNF-α) and AD biomarker (Amyloid Beta 42, Aβ42 and
tau) levels in the brain. The reduction of behavioural impairment reported for 3TgXAD mice was observed
significantly for the D3 drug dose and for all behavioural tests, when administered at 11 weeks. Similarly,
beneficial effects of antroquinonol (at higher dose D3) were noted in the transgenic mice in terms of AD
biomarkers (tau and phosphorylated-tau), systemic inflammatory (IL-1β), brain anti-inflammatory (Nrf2)
and oxidative (3-Nitrotyrosine, 3NT) markers. Improvement of memory impairment was also significantly
identified when antroquinonol (D3) was administered at late stage (9 months).
Considering both the high social and economic costs of AD in our growing elderly society, there is
an urgency to find new strategies for the prevention and treatment of this pathology. Since antroquinonol
has been utilized without adverse effects in previous successful clinical trials and is currently used for other
pathologies, its consideration as a preventive and/or therapeutic AD agent at early and/or later stage of AD
pathophysiology now appears timely and topical.
Distinguished Professor Lyn Griffiths is a molecular geneticist with more than 30 years’ research experience.
DProf Griffiths established and heads the Genomics Research Centre at QUT undertaking research focused
on identifying genes involved in common traits and disorders including migraine, cardiovascular disease,
memory, dementia and concussion. For this research she has established a significant bank of population
genomics resources including case-control, multigenerational pedigree and genetic isolate (from Norfolk
Island) cohorts. She is also Director of the Centre for Genomics and Personalised Health which aims to
discover better methods of diagnosing disease, develop targeted treatments based on genetic information,
and training the next generation of translational genomics scientists. In addition, DProf Griffiths is a
passionate advocate of the translation of medical research through commercialisation and is the Director of
the MTP Connect and industry led Bridge and BridgeTech programs, undertaking commercialisation
training for the pharmaceutical and medical devices-technology fields across Australia, respectively. Prof
Griffiths’ own genetics research at the Genomics Research Centre has led to diagnostic breakthroughs for
several neurogenetic disorders, including familial migraine, ataxia, epilepsy and hereditary stroke. Her
research has appeared in more than 400 peer-reviewed international journals and she has obtained significant
competitive and industry research funds to support her research team.
- Faculty of Health Sciences of the Federal University of Grande Dourados Foundation, Brazil
- Title:Profile of the Indigenous Epileptic Patient in a Brazilian Village
- Time :
This study aimed to characterize the nature of epileptic seizures in the indigenous population of the Jaguapirú village in the municipality of Dourados (MS), Brazil. In addition to the prevalence, we aimed to determine the nature of paroxysmal events of non-epileptic origin in this population. We believe that our study means a significant contribution to the literature because it shows that an excellent therapeutic response is achieved with first-generation antiepileptic drug monotherapy in most cases (87.7%). EEG contributed to the definition of focal epilepsies and helped in the diagnosis of patients with seizures of non-epileptic origin, among which psychogenic seizure were most frequent, followed by syncope. Vertigo predominated in the elderly aged over 60 years, while psychogenic seizures prevailed in younger patients. Epilepsy was more prevalent in the Guarani ethnic group, even though they represented less than 30% of the patients in the study, which may be related to the lower socioeconomic status of this ethnic group in relation to the others. Another expected association was home birth and epilepsy, which was not statistically confirmed. Investigating the epidemiological determinants of epilepsy in traditional communities is essential for the establishment of public policies in countries such as Brazil.
Commission on Classification and Terminology of the International League Against Epilepsy Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the. Epilepsia 1981; 22: 489–501.
Engel J Jr, International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001; 42: 796–803.
Fisher RS, Cross JH, D’Souza C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 2017; 58: 531–42.
Scheffer L, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies. Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58: 512–21.
Placencia M, Sander JW, Roman M, Madera A, Crespo F, Cascante S, Shorvon SD. The characteristics of epilepsy in a largely untreated population in rural Ecuador. Jr. Neurol Neurosurg and Psychiatr 1994; 57:320-25.
Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr 2016; 16: 48–61.
- Queensland University of Technology, Australia
- Title:Gene Profiling in Different Stages Of Alzheimer’s Disease: A Genome-Wide Study
- Time :
Alzheimer’s Disease (AD), the most common form of age-related dementia, is a progressive, neurodegenerative disease characterized clinically by a gradual cognitive decline including loss of memory, orientation and reasoning and pathologically characterized by neurofibrillary tangles and amyloid plaques in the brain. There is currently no simple definite test to diagnose AD. Hence, there is a considerable interest in reliable early detection. Despite recent progress in genetic research, gene testing is currently not sufficiently reliable for most individuals and has limited utility for predictive purposes. We here examined gene expression profiles and microRNA patterns using the Affymetrix Human Transcriptome array 2.0 in saliva in patients across several stages of AD (mild, moderate and severe) compared to a healthy control group matched for gender and age. AD patients (with diagnosis established according to NINCDS-ADRDA criteria) were classified into mild (n=8), moderate (n=7) and severe (n=7) stages of AD dependent on their clinical profiles and cognitive performance. The control group (n=19) consisted of individuals with no family history of AD. Analysis of the array data was performed in R using oligo and limma. The ratio of expression of genes between groups was reported as fold change, and a globally adjusted Benjamini Hochberg FDR of 0.1 was utilised to maximise the discovery of differentially expressed genes and pathways.
Pathway and gene-set enrichment analysis (GSEA) was performed using clusterProfiler. Results showed increased levels of differential expression between AD patients and control groups in saliva, with differentially expressed genes becoming more substantial with disease progression. Specifically, in early stage of AD, chromosome and chromatin organisation pathways were some of the most enriched in Gene Ontology GSEA when compared to controls (FDR<0.001), while immune response and cytokine pathways were most enriched when comparing both AD patients in late-stage to early-stage, and late-stage to controls (FDR<0.001). This study presents a new avenue of investigation into molecular processes occurring at the early stage of disease. The result of this research will help to gain a better understanding of the pathways implicated in AD pathophysiology at early stage of the disease and may offer a new avenue for diagnostic and/or the therapeutic development for AD. Biography
Dr Francesca Fernandez is an innovative researcher, with education and research training in both Neurosciences and Human Genetics. Her research expertise spans both mental health and neurobiological disorders, utilising a variety of approaches and contributing to knowledge of cellular, individual and population aspects of these disorders. For over 15 years, her research uses various models (DNA case-control populations, postmortem human brain tissue, cognitive testing in animal and/or human) to uncover mechanisms underlying the molecular basis of learning and memory processes in the context of healthy ageing and/or pathological disorders (dementia) and mental health (depression, schizophrenia, cannabis use). Dr Fernandez’s national and international reputation are illustrated from her numerous research collaborations, invitations to contribute to publications from diverse disciplines and her successful research funding totaling around $3 million. Her multidisciplinary approach uniquely places Dr Fernandez’s at the cutting edge of research examining the molecular basis in brain in healthy and pathological contexts.
- University hospital of Coventry and Warwickshire, U.K
- Title:Spinal Cord Tumor Presenting as Idiopathic Intracranial Hypertension-a Misdiagnosis: Case Report
- Time :
Background: Idiopathic Intracranial hypertension (IIH), is a relatively uncommon disorder characterised by raised intracranial pressure without any established pathogenesis. The symptoms are essentially of headache, nausea, vomiting, visual loss and findings of papilledema. Very rarely a spinal tumor is seen as the cause of the symptoms.
Case description: We present a 26 year old male, with BMI of 24.6, who is otherwise fit and well, that was admitted from the Emergency department with 6 days history of headache, one episode of vomiting, photophobia, neck pain, low grade fever, confusion and blurring of vision. He was initially treated by Neurologist with broad spectrum antibiotics and antiviral for suspicion of meningio – encephalitis. Later lumbar puncture with cerebro spinal fluid (CSF) analysis and MRI brain demonstrated no infective pathology. Patient had persistent headache and blurry vision and input from Ophthalmology revealed Left VI nerve palsy and bilateral papilledema. Neurologist made a differential diagnosis of IIH and venous sinus thrombosis and started him on Acetazolamide.
He did not have any significant past medical history and his BMI was not typical for IIH. The CT venogram showed no obstructive pathology or any stenosis. The lumbar puncture revealed opening pressure of 34cm H20. Reconfirmation of CSF results showed no infective aetiology and the antibiotics and antivirals were stopped. IIH was provisionally diagnosed and he was referred to Neurosurgeons for CSF diversion.
Investigation: Due to unusual presentation, we advised a full cranio-spinal MRI and it revealed a spinal cord lesion attached to the filum terminale at L1/2 level with significant compression to the thecal sac, conus and cauda equina with spinal CSF flow impairment at that level
Treatment: He underwent a Posterior T12 to L2 laminectomy and complete excision of the tumor under Neurophysiological monitoring. He improved significantly within one week of his operation with headaches and vision getting better and objectively the papilledema was also better as confirmed by the Ophthalmologist. He was discharged home and till his first follow up after 6 weeks is neurologically much better with headaches completely resolved and vision almost back to normal. The histopathology came as Ependymoma WHO grade 2.
Conclusion: For someone presenting with IIH, a spinal tumor should be considered in the differential diagnosis, especially when there is no dural venous sinus anomaly and patient refractory to medical treatment.
Keywords: Idiopathic Intracranial hypertension (IIH), Cerebro spinal fluid (CSF), Papilledema, Intradural Extramedullary
Dr. Debasish Hajra, is a Medical graduate from India and have been working in the Neurosurgery speciality in the UK for over 17 years. After completing his Membership Royal College of Surgeons (MRCS), he has worked as a registrar and subsequently got promotion as a senior registrar in Neurosurgery. He currently works in University Hospitals Coventry and Warwickshire, U.K. He had also passed his EANS (European Association of Neurosurgery Societies) exam and cleared his Fellowship Royal College of Surgeons (FRCS) part I exam. He had a special interest in Spine and Skull base.
- University of Iceland, Iceland
- Title:Sudden Unique Self-Similarity Between Human and Pre-Neuronal Intracellular Mass-Societies: Giant Extra-Individual T-Strings and the Forming of Citizens
- Time :
This presentation is mainly based on long standing biomathematical behavioral research recently described in “T-patterns, external memory and mass-societies in proteins and humans: In an eye-blink the naked ape became a string-controlled citizen” https://doi.org/10.1016/j.physbeh.2020.113146 (free open access).
Since the early 1970’s, this project was much inspired by N. Tinbergen, K. Lorenz, and K. von Frisch’s research on animal and human social behavior winning them the Nobel Prize in Physiology or Medicine in 1973, the first in Ethology, the biology of behavior. Insects were still the smallest animals studied so none were components of any others and there was no mention of nanoscale actors nor self-similarity.
The focus here has been on defining mathematical pattern types for behavior analysis, mainly the T-pattern, a hierarchical and self-similar pattern recurring with significant translation symmetry in time and on strings (T-strings) and developing (since the late 70’s) adequate computational algorithms and software (THEMETM, patternvision.com) used for their detection in humans, animals, neurons, and proteins. This has finally drawn attention to unique structural similarities between intracellular protein mass-societies and those extremely recent of humans; a self-similar hierarchy of T-pattern based mass-societies.
Nanoscale phenomena have recently become visible to humanity uncovering a highly patterned pre-neural world where billions of years ago an RNA world invented extra-individual purely informational T-strings, i.e., DNA, and soon there was only the world of DNA-based world of walking and working protein mass-societies (“Cell Cities”). Billions of years later, human mass-societies are the first and only animal societies to reach self-similarity with these DNA/protein mass-societies of every cell in their bodies, by also inventing extra-individual purely informational T-strings, i.e., TEXT and bit T-strings, and now nearly all human life is TEXT-based and mass-social with external-memory (first using clay, now mostly silicon) allowing explosive growth of human knowledge, science, and technology separating human life dramatically from any other known forms of life.
Dr. Magnus S. Magnusson, Emeritus Research Professor, he is a founder and director of the Human Behavior Laboratory, School of Health Sciences, University of Iceland. Author of the T-system and THEMETM (PatternVision). Co-directed project “DNA analysis with Theme”. Keynotes in biology, neuroscience, mathematics, science of religion, proteomics, A.I., and nanoscience. Deputy Director 1983-1988 in the Museum of Mankind of the National Museum of Natural History, Paris. Repeatedly, invited Professor at the University of Paris V, VIII & XIII. Since 1995 in formal collaboration between 32 European and American universities initiated at the University of Paris V, Sorbonne, based on “Magnusson’s analytical model”. His Main interest: mass-societies and bio-mathematical self-similarity between nano and human scales.
- University of Concepción, Chile
- Title:Covered-Stent Treatment of an Extracranial Internal Carotid Artery Pseudoaneurysm in a 3 Years-Old Child with 12-Years Follow-Up. Case Report.
- Time :
Introduction: Extracranial internal carotid artery (ICA) pseudoaneurysms in children, although uncommon, are life-threatening. Covered stents are a good alternative treatment, as they avoid the risk of open surgery and preserve the internal carotid artery. Long- term outcomes were unknown until recently. Report: In August 2008, a 3-years-old child was treated with a covered stent for a pseudoaneurysm in the extracranial ICA. A long-term follow up is presented. Results: The child was discharged with full recovery and without neurological sequelae. He has been followed-up and has remained asymptomatic for 12 years, with CTA- confirmed internal carotid artery patency, without deformation or evidence of significant re- stenosis. Conclusion: This the first report of the long-term outcome of a covered stent in a child treated at 3 years of age, with a 12-year follow-up. The good performance of the covered stent in this case reinforces its adoption as a first-line option in the treatment of extracranial ICA pseudoaneurysms in children.
Dr. Roberto Sánchez, is a Professor of Surgery
Faculty of Medicine- University of Concepción- CHILE Fellow of the American College of Surgeons.
He is a Former Foreign Resident of Paris Hospitals,He is also a Foreign Associate Member Society of Vascular and Endovascular Surgery of French Language (SCVE), Non-European Membership European Society of Vascular and Endovascular Surgery (ESVS)
- University Hospital Nuestra Señora de Candelaria, Spain
- Title:Rhombencephalitis Associated with Anti-NMDA Receptor Antibodies: An Unusual Presentation.
- Time :
Anti-NMDA receptor encephalitis mainly affects young people, often requiring a high clinical suspicion for diagnosis. The typical clinical presentation includes psychiatric symptoms, movement
disorders, seizures and dysautonomia. We present a highly unusual case where the rhombencephalon was exclusively affected, leading to a clinical expression of a pancerebellar syndrome.
A 21 year-old male individual lacking any previous relevant medical history, was hospitalised as a result of a progressive clinical picture of dizziness, cephalalgy and binocular diplopia. Physical examination showed lethargy, limited right-eye abduction, bilateral appendicular ataxia and general hyporeflexia. Complementary tests showed there was a mononuclear pleocytosis, high protein levels in the cerebrospinal fluid, and MRI revealed abnormal T2/FLAIR hyperintensity localised in pons and cerebellar hemispheres. Despite having received a treatment of intravenous immunoglobulins, the patient presented seizures and a paracerebellar syndrome. Thus, another cycle of high concentration of both immunoglobulins and intravenous steroids was required for eight days to observe a decrease of symptoms.
Further analyses conducted by an external laboratory showed the presence of anti-NMDA receptor antibodies in the cerebrospinal fluid, as well as a secondary surface antibody that still remains unknown.
This case increases the clinical spectrum of anti-NMDA receptor encephalitis. Other studies have described several cases where anti-NMDAr antibodies have caused syndromes affecting the brain stem or the cerebellum. However, solely presenting a rhombencephalitis as an initial symptom has barely been documented so far. Additionally, the impact that the secondary surface antibody that was detected in the cerebrospinal liquid might have on the patient’s pathology remains unknown. Nonetheless, several studies suggest that 4-7.5% of anti-NMDAr encephalitis could present coexistent antibodies, as this area of study continues to expand.
Dr. Miguel Solé-Sabater graduated in Medicine from the University of La Laguna in 2018. He now works as a resident of Neurology in Hospital Universitario Nuestra Señora de Candelaria, Tenerife.
He is also doing a PhD in the University of La Laguna, where he focuses on neurophysiology, by studying brain biorhythms and transcranial magnetic stimulation.
- Santa Casa Hospital of Porto Alegre, Brazil
- Title:Single Burr-Hole Extended Transforaminal Approach for Concurrent Endoscopic Surgery in the Third Ventricle Posterior to the Foramen of Monro and Ventriculostomy: Clinical Series and Planning Steps
- Time :
Objective. For endoscopic surgery of lesions in the middle to posterior third ventricle that frequently require a third ventriculostomy during the same procedure, an extended transforaminal approach (ETFA) via a single burr hole is presented. Aims of the study were to define a safe transchoroidal entry zone, to
calculate the optimal position of the burr hole, and to report the clinical results from a patient series.
Patients and Methods. Preclinical part with cadaver study (n=6 hemispheres) and retrospective MRI assessment of cases with occlusive hydrocephalus (n=30 sides). Retrospective review of clinical series of concurrent third ventricle surgery (14 cystic lesions and 11 tumor cases) and third ventriculostomy for feasibility of the endoscopic ETFA procedures and clinical outcome.
Results. The anatomical study revealed a foramen of Monro diameter of 5mm (4-7mm) and a safe entry zone of additional 5mm (3-6mm). On MRI of patients with enlarged third ventricle, the foramen of Monro diameter was 7mm (3-11mm) and the safe entry zone 6mm (3-12 mm) for the ETFA. The optimal burr hole
position was 22mm (10-30mm) lateral to the midline and 8mm (27 to -23mm) precoronal. Clinically, the ETFA was feasible in 24/25 cases. The safe entry zone was sufficient in 16 cases; the anterior septal vein was transectioned in 9 cases without clinical consequences.
Conclusion. According to our data, concurrent endoscopic surgery in the middle to posterior third ventricle and ventriculostomy are feasible via a single burr hole and a transchoroid extension of the transforaminal approach. Precise preoperative planning is recommended for assessing the individual nuances of this approach.
Keywords: ventricular endoscopy, transchoroidal approach, minimally invasive, tumors
Dr. Carlos V Brusius is a Physician specialized in Neurosurgery, he has done his MHSc in Neurosurgery at Federal University of São Paulo (UNIFESP), he obtained the PhD in Medical Sciences at Federal University of Rio Grande do Sul (UFRGS), acting on the topics of Neurosciences, Artificial Intelligence, and Oncology.
- B. P. Koirala Institute of Health Sciences, Nepal
- Title:A Rare Case of Creutzfeldt-Jakob Disease Reported from Nepal
- Time :
Creutzfeldt‐Jakob disease (CJD) is a rare disorder of the central nervous system. It is rapidly progressive and always fatal. Even in absence of typical imaging pattern, good clinical judgement along with supporting investigations can aid to the diagnosis of CJD in a setting where resources are limited.
We report a rare case of probable Creutzfeldt‐Jakob disease (CJD) in a 65‐year‐old man, probably the second case in Nepal, who initially presented with progressively increasing low mood with catatonia along with rapidly progressive dementia and features of upper motor neuron lesions. The first case of CJD from Nepal being reported by Kharel et al in 2019. Magnetic resonance imaging of brain revealed confluent areas of T2 and fluid‐attenuated inversion recovery (FLAIR) high signal intensity in bilateral fronto‐parietal deep white matter. The electroencephalogram showed bilaterally synchronous periodic pattern of bi‐ or triphasic sharp waves of 1 Hz. The patient expired at 1.5 months of diagnosis.
Creutzfeldt‐Jakob disease is a progressive, fatal neurodegenerative disease and is caused by misfolded, transmissible proteinaceous infections particles, or prions. Although the concentration of CJD prions varies throughout the body of an infected individual, it is highest in the brain and the posterior eye (retina and optic nerve), resulting in neurological symptoms, including rapidly progressing dementia, cerebellar and extrapyramidal signs, and myoclonus and visual symptoms. The life expectancy of most people clinically diagnosed with CJD is 1 year from the onset of symptom. Among the three major groups of human prion disease: sporadic, genetic, and acquired; sporadic CJD (sCJD) is most common, accounting for about 85% of CJD cases. With the occurrence generally in late middle age at a mean age of 67 years, they have a short survival post‐diagnosis of about 4 months. However, at least six different clinic‐pathological CJD subtypes with variable presentations are known. Even with the evidence of a genetic predisposition to sCJD, the precise cause of the disorder is unknown. The global incidence of CJD is typically reported to be around 1–2 cases per million per year.
We present a case report that includes the clinical and radiological features of the probably second case of CJD in Nepal, and also illustrates the complexity of diagnosing this disease in a resource‐limited setting.
Dr. Durga Neupane, had completed Bachelor of Medicine and Bachelor of Surgery(MBBS) from B.P. Koirala Institute of Health Sciences, Dharan, Nepal. He has been currently enrolled in Bachelor of Science in Neurosurgery in Abdulrauf University of Neurosurgery, USA, a first online university of Neurosurgery. He has been accepted by Harvard Medical School, Boston, USA for Foundations of Clinical Research, Class of 2022 with a scholarship. He has been appointed as an official peer reviewer and editorial board member of few international medical journals. He has core interest in Neurosurgery and has published about 20 research articles in Neuroscience. He attended World Congress of Neurosurgery in 2021. He is fluent in Nepali, English and Hindi languages. He enjoys literature and football. He has attended a national level conference on mental health which was organized jointly by WHO and Ministry of Health and Population of Nepal. He is an active member of Walter E Dandy Neuro Club of Nepal. He has been serving as a primary care physician in a rural municipality of Eastern Nepal. Recently, he conducted a free mega health camp at a countryside, the report of which is published in international journal.
- SVIMS, INDIA
- Title:Cisternostomy vs Decompressive Craniectomy for The Management of Traumatic Brain Injury: A Randomized Controlled Trial
- Time :
Background: Goal of treatment in the management of traumatic brain injury (TBI) is to
avoid the secondary brain injury. Though decompressive craniectomy has shown to reduce
ICP but in reality, it provides an outlet for brain tissue to expand only without reducing the
oedema. Basal Cisternostomy (BC) is an emerging microsurgical technique in the
management of cerebral oedema in TBI. By this technique, CSF is let out from basal cisterns
which reduces cerebral oedema. In this study we compared the outcomes of Cisternostomy
with decompressive craniectomy and studied the effectiveness of Cisternostomy in
decreasing cerebral oedema. This is the first Randomized controlled trial on comparing the
Cisternostomy with decompressive craniectomy
Methods: All the enrolled patients were randomised into 2 groups. They were assessed
clinically and radiologically. Categorised into mild, moderate and severe head injury groups
and Marshall CT score was given. Intraoperative ICP was measured in both the groups.
Outcomes were assessed with the factors like post-operative ICU care, days on ventilator
support and GOS score.
Results: 50 patients were randomized into 2 groups with 25 patients each. Mortality rate in
this study was 32% (8) in Cisternostomy group whereas it was 44% (11) in decompressive
craniectomy group. There was decreased mean days of ventilator support and ICU care
requirement in Cisternostomy group. Cisternostomy causes significant decreases in ICP after
craniotomy. Age, time interval from trauma to surgery and Marshall CT score showed
prognostic importance on outcomes.
Conclusion: Cisternostomy was effective in reducing the ICP in the traumatic brain injury
patients. With Cisternostomy there is good GOS and low rate of complications in the postoperativeperiod. Age, presenting GCS, Marshall CT score, association with other major
injuries and time interval from trauma to surgery had a significant prognostic impact on the
outcome in the management of traumatic brain injury.
Dr. Hanuma Naik Banavath is an Assistant Proffessor, MS, Mch – NEUROSURGERY
SVIMS, TIRUPATHI, ANDHRA PRADESH, INDIA
He gained his Mch – Neurosurgery from SVIMS, Tirupati, A.P, He also obtained his MS – General surgery from PGIMER, Chandigarh. He completed his MBBS from NRI medical college, Chinakakani, Guntur dist., A.P
He is an Assistant professor – Neurosurgery from September 2021 – present
SVIMS, Tirupati. He also served as a Senior resident in Neurosurgery (non-academic, after MS) from Sep 2017 – Aug 2018, GMCH-32, Chandigarh.
His Publications are:
1. Cisternostomy vs Decompressive Craniectomy for The Management of Traumatic Brain Injury: A Randomized Controlled Trial – World Neurosurgery published as corresponding author
2. Outcomes and predictors of outcome with cisternostomy in the management of traumatic brain injury – a prospective observational study at tertiary centre – Indian journal of neurotrauma (original article)
2. Spontaneous rapid resolution of acute subdural hematoma: revelation in the era of modern science – Indian journal of neurotrauma (case report)
Under review as corresponding author
1. Percutaneous surgical approach for vertebral compression fractures – Predictors of Outcome: 5 Years of Experience at A Tertiary Care Center – Indian journal of neurotrauma
- King's College London, UK
- Title:Choroid Plexus Enlargement is Associated with Neuroinflammation and Reduction of Blood Brain Barrier Permeability in Depression
- Time :
Background: Depression is often associated with elevations of peripheral inflammatory markers. The mechanisms linking peripheral inflammation and changes in the central nervous system in MDD are still under investigation. Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in brain homeostasis and mediating the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with central brain inflammation.
Methods: 51 depressed participants (HDRS score >13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. We leveraged transcriptomic data from the Allen Human Brain Atlas (AHBA) to explore possible associations between the brain map depicting the correlations between CP volume and TSPO and functional brain pathways.
Results: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) =
+2.17, p=0.03) that was positively correlated with [11C]PK11195 binding in the anterior cingulate cortex (r=0.28, p=0.02), prefrontal cortex (r=0.24, p=0.04), and insular cortex (r=0.24, p=0.04). The CP volume exhibited a negative association with the blood-to-CSF radiotracer exchange parameters (r=- 0.28, p=0.02). Integration of transcriptomic data from the AHBA with the brain map, we found significant gene enrichment for several pathways involved in neuroinflammatory response.
Conclusion: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component.
The BIODEP study was sponsored by the Cambridgeshire and Peterborough NHS Foundation Trust and the University of Cambridge and funded by a strategic award from the Wellcome Trust. Recruitment of participants was supported by the National Institute of Health Research (NIHR) Clinical Research Network. We gratefully acknowledge all study participants and the King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia, and the Saudi Arabia Cultural Bureau (SACB).
Dr. Noha Althubaity is a PhD candidate in neuroimaging research at King’s College London. A teaching assistant at Radiology department, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. She earned her bachelor’s degree in Radiological Sciences at King Saud University (Riyadh, Saudi Arabia) and the master’s degree in Radiologic and Imaging Sciences at Thomas Jefferson University (Philadelphia, USA). She is registered as a Radiologic Technologist Saudi Commission for Health Specialties and as Magnetic Resonance Imaging Technologist from The American College of Radiology and The American Society of Radiologic Technologist, ST. Paul, Minnesota (ARRT). Area of interest is the glymphatic system and depression.
Her Publications are:
• Increased serum peripheral C-reactive protein is associated with reduced brain barriers permeability of TSPO radioligands in healthy volunteers and depressed patients: implications for inflammation and depression
• Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression
- Dalhousie University, Canada
- Title:Do Symptoms of Depression and Anxiety Contribute to Heavy Episodic Drinking? A 3-Wave Longitudinal Study of Adult Community Members
- Time :
Alcohol misuse, depression, and anxiety are major public health problems (Whiteford et al., 2013). One form of alcohol misuse is heavy episodic drinking (HED) – the consumption of five + drinks (four + for women) on a given occasion (Wechsler & Austin, 1998). HED has massive economic/health costs (e.g., $223.5 billion in costs; 80,000 deaths in the US in 2006; Bouchery, Harwood, Sacks, Simon, & Brewer, 2006; Gonzales et al., 2014).
Longitudinal associations between HED and internalizing symptoms are explained in several ways. The self-medication hypothesis posits individuals use alcohol to manage their internalizing symptoms (Khantzian, 1997; Stewart, Grant, Mackie, & Conrod, 2016). Alternatively, HED may present a risk for depression or anxiety through the effects of alcohol on the brain and/or negative social consequences. The issue of directionality/temporal precedence is far from settled.
Using a 3-wave, 3-variable cross-lagged panel model, we conducted a stringent test of either internalizing symptom’s effects on HED, and vice versa, after controlling the stability inherent in each construct over time. This model was tested in a community adult sample (N = 102) in a longitudinal study with measurements at baseline, 3 months, and 6 months.
The results suggest that depressive symptoms and anxiety symptoms significantly predict HED in opposite directions over time, and that HED does not significantly predict either type of internalizing symptom over time. Specifically, greater depressive symptoms were associated with greater HED over a 3-month period after adjusting for anxiety symptoms. Anxiety symptoms were negatively predictive of HED after accounting for depressive symptoms. We also found strong temporal stability in levels of HED, depressive symptoms, and anxiety symptoms over time.
Among community-recruited adults, increased depressive symptoms were related to more HED in a subsequent 3-month period after controlling anxiety symptoms, whereas increased anxiety symptoms were related to less HED over this timeframe after controlling depressive symptoms. Although this suggests support for the self-medication hypothesis, additional investigations are needed. Limitations of the study, future research, and clinical implications will be discussed.
Dr. Dayna Lee-Baggley is a Registered Clinical Psychologist in Nova Scotia, Canada. She is the director of Dr. Lee-Baggley and Associates, a virtual health psychology clinic specializing in clinical interventions, training for healthcare providers, and research in health-related issues (e.g., chronic pain, sleep, COVID burnout, PTSD for frontline workers). She worked for almost 15 years in multidisciplinary teams on medical, surgical and cancer care hospital units providing assessment, therapy and consultation for patients with chronic and life-threatening health conditions. She also conducts research as an Assistant Professor in the Department of Family Medicine, with a cross appointment in the Department of Psychology & Neuroscience at Dalhousie University and an Adjunct Professor appointment in the Department of Industrial and Organizational Psychology at Saint Mary’s University. She has an active research program on behavior change, obesity, chronic disease, professional resiliency, workplace mental health and Acceptance and Commitment Therapy. Dr. Lee-Baggley has close to 45 peer-reviewed publications and over 130 scholarly presentations. She is a senior consultant providing healthy workplace interventions for employees, teams, and leaders with Howatt HR Consulting and the Chief of Research for the Howatt HR Applied Workplace Research Institute. She is an internationally recognized trainer in Acceptance and Commitment Therapy and a certified therapist in Emotion Focused Therapy for Couples. She was the recipient of the 2017 Women of Excellence Award for her contributions to Health, Sport and Wellness (Canadian Progress Club Halifax Cornwallis). She is the author of the book “Healthy Habits Suck: How to get off the couch & live a healthy life…even if you don’t want to.”
- Ibn Rochd University Hospital Center, Morocco
- Title:An Atypical Protuberantial Lesion Revealing a MOG Antibody Disease
- Time :
MOG antibody disease is a recently discovered demyelinating autoimmune disease of the central nervous system, involving anti-Myelin Oligodendrocyte Glycoprotein auto-antibodies (anti-MOG). There are different clinical and radiological aspects of this pathology. The most frequent and typical one is a retrobulbar optic neuritis, predominant on the anterior region of the optic nerve, without damage to the optic chiasma and optical strips. Brain damage is less common and the spinal cord involvement may be similar to that of Devic’s disease. Nevertheless, certain radiological manifestations may be atypical and therefore are not guiding the diagnosis. We encountered in our radiology department one of these atypical cases, a 42-year-old patient without any particular pathological history who consults for a symptomatology that has been evolving for 2 months, made up of pseudo-migraine headaches associated with pain when the eyeballs are mobilized, without loss of visual acuity. A cranio-orbital MRI was performed, objectifying the presence of retrobulbar optic neuritis and a single protuberantial lesion, median anterior, with no other cerebral or spinal anomaly. A demyelinating disease was suspected and the dosage of the various auto-antibodies, in particular the anti-MOGs, was positive for the latter.
Dr Fadil Khaoula obtained her MD in the field of the Limbic system imaging in 2019 at Ibn Rochd university Hospital Center of Casablanca (Morocco) where she is currently a 4th year resident in radiology. During her formative years, she has been interested in neuro-radiology, mainly in demyelinating diseases and their atypical radiological manifestations. She is a member of the Moroccan and French society of radiology, with works (articles, posters) published and in the process of being published in the field of neuro-radiology.
- Georgia State University, USA
- Title:Classifying Handedness with MRI
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When aggregating neuroimaging data across many subjects, an important consideration is establishing some group-level uniformity prior to further statistical analysis. Spatial normalization and motion correction are two important preprocessing steps that help achieve this goal. Researchers have also often excluded left-handed subjects due to presumptions about variable asymmetries relating to both brain structure and function, which may interfere with achieving a desired level of group homogeneity. It is well-known, however, that hand-preference is not a binary attribute and is not a perfect representation of structural asymmetry or hemispheric specialization. In an effort to demonstrate a more objective, data-driven approach for quantifying asymmetries across handedness, we tested the reliability of single-subject classification of handedness using data obtained from structural MRI in extant samples. We utilized data from deformation fields created during the spatial normalization process within a priori regions of interest (ROIs), including the motor and somatosensory cortex, and Broca’s and Wernicke’s areas. Using these deformation fields as features in machine learning classifiers, we achieved classification accuracies greater than 75% across two independent datasets (i.e., a sample of incarcerated adult offenders and a sample of community adults from the Netherlands). These results demonstrate reliability of morphological features attributable to handedness as represented in neuroimaging data and further suggest that application of data-driven techniques may be a principled approach for addressing asymmetries in group analysis.
Mr. Sandeep Panta is a Full Stack Engineer at TReNDS Center, Georgia State University. He has experience with creating easy-to-use tools for pre-processing neuroimaging data, data harmonization, big data visualization tools, machine learning, federated learning software to facilitate big data collaborative research that would not be possible otherwise. He has published two papers as first author: “A tool for interactive data visualization: application to over 10,000 brain imaging and phantom MRI data sets“ and “Classifying handedness with MRI“. His present work includes federated learning and differential privacy using COINSTAC software. He has co-authored 6 papers on the same. TReNDS Center is focused on developing, applying and sharing advanced analytic approaches and neuroinformatics tools that leverage advanced brain imaging and omics data, with a goal of translating these approaches into biomarkers that can help address relevant areas of brain health and disease. Large scale data sharing and multimodal data fusion techniques are the underpinnings of their approach.
- Iran University of Medical Sciences, Iran
- Title:Protective Effect of N-Acetyl Cysteine on Mitochondrial Dynamic Imbalance In Temporal Lobe Epilepsy: Possible Role of Mtor
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Epilepsy is a neurological disorder, and understanding the underlying molecular mechanisms is critical for the development of more effective therapies. It is believed that mTOR (Mechanistic Target of Rapamycin kinases) activity and the mitochondrial dynamic balance change during epilepsy. mTOR affects mitochondrial fission by stimulating the translation of mitochondrial fission process 1 (MTFP1). In this study, the protective role of N-acetylcysteine was studied in temporal lobe epilepsy (TLE) through the regulation of mTOR and mitochondrial dynamic proteins. Rats received N-acetylcysteine (oral administration) seven days before induction of epilepsy, followed by one day after epilepsy. TLE was induced by microinjection of kainite into left lateral ventricle. The total mTOR and Drp1 levels were detected in the hippocampus by western blotting. MFN1 was assessed using immunohistochemistry, and the expression of Fis.1 and MTFP1 (fission-related proteins) and OPA (fusion-related protein) was detected by real time PCR. The mitochondrial membrane potential was measured by Rhodamin 123. The results showed that 72 h after induction of epilepsy, the mTOR protein level increased, and the balance of the mitochondrial dynamic was disturbed; however, oral administration of NAC decreased the mTOR protein level and improved the mitochondrial dynamic. We concluded that NAC plays a neuroprotective role in temporal lobe epilepsy, probably through decreasing the mTOR protein level, which can improve the imbalance in the mitochondrial dynamic.
Farnaz Nikbakht, before obtaining her PhD degree in Human Physiology from Shiraz University in 2007, she received an award from the Iran Ministry of Health and Education; she spent six months at Flinders University, Adelaide, Australia for completing her research on degenerative diseases. Now, as the Professor of Department of Physiology, Iran University of Medical Sciences, she has managed several research programs and has conducted the thesis of several Masters and PhD students in her Lab. Since 2010 she has directed a research team on Epilepsy and Alzheimer’s diseases fields in her lab. Her research leads to publishing several articles.
- Sacred Heart Psychiatric Institute, Ecuador
- Title:Factors Associated with Psychiatric Adverse Effects in Healthcare Personnel during the COVID-19 Pandemic in Ecuador
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Since the emergence of respiratory syndrome caused by the novel Coronavirus (COVID-19), the world has faced a pandemic with consequences at all levels. In many countries, the health systems collapsed, and the healthcare professionals had to be on the front line of this crisis. The adverse effects on the mental health of healthcare professionals have been widely reported. This research focuses on identifying the main factors associated with adverse psychological outcomes.
Method: Descriptive, cross-sectional study, based on surveys, applying the PHQ-9, GAD-7, ISI and EIE-R tests to healthcare professionals from Ecuador during the COVID-19 pandemic.
Results: 1028 participants, distributed in 557 physicians (54.18%), 349 nurses (33.94%), 29 laboratory workers (2.82%), 27 paramedics (2.62%), 52 psychologists (5.05%) and 14 respiratory therapists (1.36%). From 16 of the 24 provinces of Ecuador. 27.3% presented symptoms of depression; 39.2% anxiety symptoms; 16.3% insomnia and 43.8% symptoms of PTSD, the 4 types of symptoms in ranges from moderate to severe. The most relevant associated factors were: working in Guayas (the most affected province) (OR: 2.18 for depressive symptoms and 2.59 for PTSD symptoms); be a postgraduate doctor (1.52 for depressive symptoms and 1.57 for insomnia), perception of not having the proper protective equipment (OR: 1.71 for symptoms of depression and 1.57 for symptoms of anxiety) and female sex (OR: 1.39 for anxiety)
Discussion and Conclusions: Healthcare professionals have a significant impact on their mental health that may require psychiatric and psychological intervention. The main risk factors are mainly related to geographical distribution and job characteristics, such as being a resident physician and self-perception of safety. Further studies are required based on the evolution of the pandemic.
- University of Sfax, Tunisia
- Title:Effect of Nighttime Melatonin Ingestion on Dynamic Postural Balance and Muscle Strength in Persons with Multiple Sclerosis: A Controlled-Randomized Trial
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Objective: To investigate the safety and the effect of nocturnal MEL ingestion on dynamic postural control the following morning in adults with MS.
Methods: Fourteen adults with mild relapsing-remitting (RR-MS) (28.36 ±6.81 years) were assessed before and after nocturnal ingestion of 6-mg MEL or placebo (PLA). A posturographic test in eyes opened condition (EO) was used to evaluate dynamic postural balance in in mediolateral and anteroposterior axis. Leg muscles strength, nociceptive and neuropathic pains, were evaluated by using the 5-sit to stand test (5-STST), the visual analogue scale (VAS) and the neuropathic pain 4 questions (DN4), respectively. Hooper index was used to evaluate sleep quality, fatigue, stress and muscle soreness.
Results: MEL decreased posturographic parameters [center of pressure (CoP) path length (CoPL), CoPL in anteroposterior axis (CoPLY), mean CoP velocity (CoPVm)], more than PLA by 7.56% (p=0.02), 19.27% (p=0.000001), 11.1%, (p=0.00003) respectively, in mediolateral axis, and by 9.1% (p=0.005), and 4.29% (p=0.025), respectively in anteroposterior axis. MEL reduced duration of 5-STST, VAS and DN4 scores more than PLA by 8.19% (p=0.008), 84.44% (p=0.04) and 37.69% (p=0.023), respectively. MEL enhanced fatigue and sleep quality more than PLA by 42.29% (p=0.044) and 30.2% (p=0.012). No significant difference was observed between MEL and PLA intake in stress and muscle soreness.
Conclusion: Acute MEL ingestion enhanced dynamic postural stability and lower-limb muscle strength via improving pains, fatigue and sleep quality in RR-MS adults. Since only the effect of single-dose of MEL was evaluated in this study, these results are recommended only for short-term use.
I am Sonda jallouli, 25 years old, a physiotherapist from the promotion of 2017. Currently, I am a PhD student in the biological sciences of physical and sports activities at the Higher Institute of Physical Education Sports in Sfax, Tunisia. My field of research is in neurological diseases (multiple sclerosis), physical disorders, gender differences, chronobiology, supplementation, sleep, cognitive functions, training, biochemistry, physiological adaptation, psycho-cognitive performance.
- Brigham and Women's Hospital, USA
- Title:How Self-Reported Hot Flashes May Relate to Affect, Cognitive Performance and Sleep
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Purpose: To explain the controversy about whether midlife women who self-report hot flashes have relatively increased affective symptoms, poor cognitive performance or worse sleep. Methods: Retrospective data from 88 women seeking relief from bothersome day and night hot flashes were submitted to mixed linear regression modeling to find if estimated hot flashes, as measured by Women’s Health Questionnaire (WHQ) items or diary-documented hot flashes recorded daily were associated with each other or with affective, cognitive or sleep measures. Results: Subjects averaged 6.3 daytime diary-documented hot flashes and 2.4 nighttime diary-documented hot flashes per 24 h. Confounder-controlled, diary-documented hot flashes but not estimated hot flashes were associated with increased Leeds anxiety scores (F = 4.9; t = 2.8; p = 0.01) and Leeds depression scores (3.4; 2.5; 0.02), decreased Stroop Color–Word test performance (9.4; 3.5; 0.001), increased subjective sleep disturbance (effect size = 0.83) and increased objective sleep disturbance(effect size = 0.35). Hot flash effects were small to moderate in size. Univariate but not multivariate analyses revealed that all hot flash measures were associated with all affect measures. Different measures of hot flashes associated differently with affect, cognition and sleep. Only nighttime diary-documented hot flashes consistently correlated with any affect measures in multivariate analyses.
Conclusions: Reported inconsistencies in menopause study outcomes may be due to the use of differing measures for hot flashes, affect, cognition and sleep. This problem impedes forging a consensus on whether hot flashes correlate with neuropsychological symptoms.
Dr. Quentin Regestein is a clinician-researcher interested in menopause and transcranial brain stimulation. He currently develops applications to improve US health care delivery.
- University of Missouri, Columbia
- Title:Enhanced Recovery: Post-Operative Delirium and Potential Interventions
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Enhanced recovery programs have been developed to improve patient’s post-operative outcomes through pre-op education and preconditioning, modification of anesthetic techniques intraoperatively and multimodal pain management techniques post-operatively. The overall goal of these protocols is to decrease the use of medical interventions and time in the hospital. With a growing elderly population requiring surgical intervention, the impact of post-operative delirium and cognitive dysfunction is a growing problem and significantly increases the cost of care. The collaborative efforts of Neurology and Anesthesiology to identify patients who are at risk and modify anesthetic techniques are the next evolution for enhanced recovery protocols to improve patient outcomes and increase efficient delivery of care.
Dr. Quinn L. Johnson is the Chair of the Department of Anesthesiology at the University of Missouri-Columbia, and serves as the Russel B. and Mary D. Sheldon Professor in Anesthesiology. He also serves as adjunct faculty in the School of Business where he teaches management classes on healthcare as it relates to business. Clinically he has advanced training in acute pain management and ultrasound guided regional nerve block techniques. Clinically he works at the Missouri Orthopaedic Institute. He recently served as the president of the Missouri Society of Anesthesiology and is currently a member of the American Society of Anesthesiology’s committee on Academic Anesthesiology. He has received grants, published and presented in numerous journals and conferences, on a variety of topics including enhanced recovery and post-operative delirium in the elderly.