Статті в журналах з теми "Neurological Disorder - Gold Nanoparticle"

Nose to brain delivery is an alternative and efficient way of delivery of drugs, protein, peptides, DNA, RNA, and plasmids for improved therapeutics in the treatment of neurological disorders. Nanotechnology enables the use of nanocarriers, such as polymer, lipid, and metal-based for delivery of an active agent to targeted site selectively and minimise other systemic side effects. Viral vectors like herpes simplex, adenovirus, and lentivirus are also used for the delivery of genes to the brain with improved transfection efficiency and transduction process. Metal-based nanomaterials such as gold and super magnetic iron oxide nanoparticles, used for theranostic application for brain-related nose to brain delivery, has proven several advantages and are discussed together with their limitations, in this review in detail.

Gold has always been regarded as a symbol of nobility, and its shiny golden appearance has always attracted the attention of many people. Gold has good ductility, molecular recognition properties, and good biocompatibility. At present, gold is being used in many fields. When gold particles are as small as several nanometers, their physical and chemical properties vary with their size in nanometers. The surface area of a nano-sized gold surface has a special effect. Therefore, gold nanoparticles can, directly and indirectly, give rise to different biological activities. For example, if the surface of the gold is sulfided. Various substances have a strong chemical reactivity and are easy to combine with sulfhydryl groups; hence, nanogold is often used in biomedical testing, disease diagnosis, and gene detection. Nanogold is easy to bind to proteins, such as antibodies, enzymes, or cytokines. In fact, scientists use nanogold to bind special antibodies, as a tool for targeting cancer cells. Gold nanoparticles are also directly cytotoxic to cancer cells. For diseases caused by inflammation and oxidative damage, gold nanoparticles also have antioxidant and anti-inflammatory effects. Based on these unique properties, gold nanoparticles have become the most widely studied metal nanomaterials. Many recent studies have further demonstrated that gold nanoparticles are beneficial for humans, due to their functional pharmacological properties in a variety of diseases. The content of this review will be the application of gold nanoparticles in treating or diagnosing pressing diseases, such as cancers, retinopathy, neurological diseases, skin disorders, bowel diseases, bone cartilage disorders, cardiovascular diseases, infections, and metabolic syndrome. Gold nanoparticles have shown very obvious therapeutic and application potential.

Stroke, one of the leading causes of death around the globe, is expected to rise considerably by 2050. The expanding nanotechnology science offers a promising future for medical research treating stroke. Nanomaterials are expanding their application in stroke management by structure and function as in perfluorocarbon, iron oxide nanoparticles, gold nanoparticles, dendrimers, quantum dots, nanospheres, and other organic and inorganic nanostructures. Nanotechnology integrated with stem-cell therapy is a different hit in stroke treatment. Nonetheless, some challenges must be resolved before globalizing the use of nanomaterials in stroke treatment and other neurological disorders.

Sepsis is a grave systemic condition that affects several organs and is caused by an infectious disease. Among the organs targeted by sepsis is the brain, a condition named sepsis-associated encephalopathy (SAE). Epidemiological studies indicate that 25%–70% of sepsis patients develop SAE, presenting acute and chronic symptoms. The main acute symptom is delirium, while chronic symptoms include cognitive impairment, locomotor dysfunction and mood disorders, amongst them, depression. The physiopathology of SAE involves systemic and local actions. Systemically, reduced brain perfusion, hyperglycemia, and activation of the sensory vagus nerve contribute to SAE. Locally, inflammation, enhanced oxidative stress, and enhanced excitotoxicity play vital roles in SAE development. Today, there is no commercially available treatment for SAE. We recently demonstrated that twenty-nanometer citrate-capped gold nanoparticles (cit-AuNP) intravenously injected two or four hours after induction of sepsis could reduce cerebral inflammation in mice. In the present study, we showed that cit-AuNP acutely injected in mice with sepsis exhibited faster clinical symptom resolution and reduced glutamate levels in the brain thirty days after sepsis induction. The acute twenty-nanometer cit-AuNP treatment also prevented depression-like behavior in mice after a sepsis episode. Thus, cit-AuNP therapy may potentially be used to prevent sepsis-induced depression.

Nanotechnology is a rapidly growing industry where nanomaterials are used in almost every field, including electronics, cosmetics, engineering, household products, biotechnology and medicine. Nanoparticles (NPs) have unique physical and chemical properties, which may cause potential hazards to human health, especially with constant exposure. Various studies have shown that NPs can enter the human body either through the respiratory tract, dermal absorption or via the gastrointestinal system and have the potential to cause respiratory disorders, behavioral changes, neurological disorders, as well as cancer. This review focuses on the health implications of NPs, specifically gold, silver, silica, titanium dioxide, aluminum, aluminum oxides, metal organic frameworks (MOF), aerosol particles, flame retardants, quantum dots, and carbon nanotubes. Herein, we discuss the routes of exposure and the impact of these nanoparticles on human health. We also summarize in-vitro and in-vivo studies that analyze the cytotoxicity profile and the associated health impact of these nanoparticles. This study could be utilized to develop well-defined guidelines for setting exposure limits for different NP types as well as a summary of related characteristics such as size, shape, morphology, and surface charge.

Objective: Neurofilament light has shown promise as a biomarker for diagnosis, staging and prognosis in a wide range of neurological and neurodegenerative disorders. This study explored the utility of cerebrospinal fluid neurofilament light in distinguishing primary psychiatric disorders from neurodegenerative and neurological disorders, a common diagnostic dilemma for psychiatrists and neurologists. Methods: This cross-sectional retrospective pilot study assessed cerebrospinal fluid neurofilament light on patients referred to a tertiary neuropsychiatry service from 2009 to 2017 for diagnostic assessment of neuropsychiatric and neurocognitive symptoms, where a neurodegenerative disorder was a differential diagnosis, who received lumbar punctures as part of a comprehensive workup. The most recent gold-standard clinical consensus diagnosis was categorised into psychiatric disorder or neurodegenerative or neurological disorder. Data from healthy controls were available for comparison. Data extraction and diagnostic categorisation was blinded to neurofilament light results. Results: A total of 129 participants were included: 77 neurodegenerative or neurological disorder (mean age 57 years, including Alzheimer’s dementia, frontotemporal dementia), 31 psychiatric disorder (mean age 51 years, including schizophrenia, major depressive disorder) and 21 healthy controls (mean age 66 years). Neurofilament light was significantly higher in neurodegenerative or neurological disorder (M = 3560 pg/mL, 95% confidence intervals = [2918, 4601]) compared to psychiatric disorder (M = 949 pg/mL, 95% confidence intervals = [830, 1108]) and controls (M = 1036 pg/mL, 95% confidence intervals = [908, 1165]). Neurofilament light distinguished neurodegenerative or neurological disorder from psychiatric disorder with an area under the curve of 0.94 (95% confidence intervals = [0.89, 0.98]); a cut-off of 1332 pg/mL was associated with 87% sensitivity and 90% specificity. Conclusion: Cerebrospinal fluid neurofilament light shows promise as a diagnostic test to assist with the often challenging diagnostic dilemma of distinguishing psychiatric disorders from neurodegenerative and neurological disorders. Further studies are warranted to replicate and expand on these findings, including on plasma neurofilament light.

Metallic nanoparticles are of great importance because of their unique physical, chemical, antimicrobial, diagnostic, therapeutic, biomedical, sensing, biosensing, catalytic and optical properties. Detailed knowledge of the atomic scale structure of these materials is essential for understanding their activities and for exploiting their potential. This paper reports structural studies of silica-supported silver, gold, palladium and platinum nanoparticles using X-ray diffraction and high-resolution transmission electron microscopy. Electron microscopy observation allowed the determination of nanoparticle sizes, which were estimated to be in the range of 45–470 Å, and their distribution. The obtained histograms exhibit a multimodal distribution of the investigated nanoparticle sizes. The X-ray diffraction data were analyzed using the Rietveld method in the form of Williamson–Hall plots, thePDFguifitting procedure and model-based simulation. The Williamson–Hall plots provide evidence for the presence of strain in all investigated samples. ThePDFguifitting results indicate that the investigated nanoparticles consist of atomic clusters with different sizes and degrees of disorder as well as slightly different lattice parameters. The detailed structural characterization performedviamodel-based simulations proves that all samples exhibit a face-centered cubic type structure with paracrystalline distortion. The degree of disorder predicted by the paracrystalline theory is correlated with the sizes of the nanoparticles. The catalytic properties of the investigated noble metals are discussed in relation to their disordered structure.

Nanomedicine compounds containing nanoparticles, such as iron oxides and gold, have been demonstrated to be effective in promoting different magnitudes of interaction with amyloid β fibrils, of which disintegrating or inhibiting effects are of great importance to treating fibrillary aggregation-induced neurological disorders such as Alzheimer’s disease. This research herein studies the interaction between lysozyme amyloid fibrils, a type of fibers derived from hen egg white lysozyme, and Fe3O4 magnetic nanoparticles (MNPs) of an assorted diameter sizes of 5 nm, 10 nm and 20 nm, using atomic force microscopy (AFM). Specifically, the effects of the sizes of negatively charged MNPs on the resultant amyloid fibrillary mixture was investigated. Our results of AFM images indicated that the interaction between MNPs and the fibrils commences immediately after adding MNPs to the fibril solution, and the actions of such MNPs-doped fibrillary interplay, either integration or segmentation, is strongly dependent on the size and volume concentration of MNPs. In the cases of 5 nm and 20 nm particles of equivalent volume concentration, the adsorption and agglomeration of MNPs onto the fibrillary surfaces was observed, whereas, interestingly, MNPs with diameter size of 10 nm enables segmentation of the slender fibrils into debris when a proper implemented volume concentration was found, which signifies utter destruction of the amyloid fibrillary structure.

Recent research points to mesenchymal stem cells’ potential for treating neurological disorders, especially drug addiction. We examined the longitudinal effect of placenta-derived mesenchymal stromal-like cells (PLX-PAD) in a rat model for cocaine addiction. Sprague–Dawley male rats were trained to self-administer cocaine or saline daily until stable maintenance. Before the extinction phase, PLX-PAD cells were administered by intracerebroventricular or intranasal routes. Neurogenesis was evaluated, as was behavioral monitoring for craving. We labeled the PLX-PAD cells with gold nanoparticles and followed their longitudinal migration in the brain parallel to their infiltration of essential peripheral organs both by micro-CT and by inductively coupled plasma-optical emission spectrometry. Cell locations in the brain were confirmed by immunohistochemistry. We found that PLX-PAD cells attenuated cocaine-seeking behavior through their capacity to migrate to specific mesolimbic regions, homed on the parenchyma in the dentate gyrus of the hippocampus, and restored neurogenesis. We believe that intranasal cell therapy is a safe and effective approach to treating addiction and may offer a novel and efficient approach to rehabilitation.

Ischemic stroke, a significant neurovascular disorder, currently lacks effective restorative medication. However, recently developed nanomedicines bring renewed promise for alleviating ischemia’s effects and facilitating the healing of neurological and physical functions. The aim of this systematic review was to evaluate the efficacy of nanotherapies in animal models of stroke and their potential impact on future stroke therapies. We also assessed the scientific quality of current research focused on nanoparticle-based treatments for ischemic stroke in animal models. We summarized the effectiveness of nanotherapies in these models, considering multiple factors such as their anti-inflammatory, antioxidant, and angiogenetic properties, as well as their safety and biodistribution. We conclude that the application of nanomedicines may reduce infarct size and improve neurological function post-stroke without causing significant organ toxicity.

IntroductionWe present a case of a 15 year-old boy diagnosed with Unspecified Personality and Beheavioral Disorder Due to Brain Damage from a Human Herpes Virus-6 Encephalitis.ObjectivesTo describe a case of an Unspecified Organic Personality and Behavioral Disorder secondary to brain damage from Human Herpes Virus-6 (HHV-6) Encephalitis in an 11 year-old childand to review recent literature, in order to improve clinical practice.MethodsClinical case report and brief review of literature. A bibliographic research was made in the database PubMed, using the terms “Viral Encephalitis” AND “Neuropsychiatric symptoms”; “Viral Encephalitis” AND “Behavioral Disorder”; “Long-Term Neurological Morbidity” AND “Viral Encephalitis”.Results15 year-old boy diagnosed with Unspecified Personality and Beheavioral Disorder Due to Brain Damage from a Human Herpes Virus-6 Encephalitis, secondary to immunosupression in the context of haematopoietic progenitor transplantation (HPT) at 11 years old. MRI showed supratentorial ventriculomegaly, atrophic changes in encephalon and right hippocampus with subcortical retraction secondary to previous encephalitis. Clinically, main changes appeared in behavior, presenting a serious frontal syndrome with high disinhibition, what implied severe social and academic difficulties. During the outpatient follow-up, the behavioural disorder is being pharmacologically treated with Risperidone 1,5mg per day with a partially favorable evolution. The patient presented intolerance to olanzapine, with an episode of low level of conciuosness after taking it.Bibliographic research results indicate that the gold standard treatment for behavioral disturbances are antipsychotics. Risperdidone is proven save for treatment in children. Results point out also the importance of an early multidisciplinar intervention, involving family training, rehabilitation resources and curricular adaptations.Image:Image 2:ConclusionsViral encephalitis may have serious neuropsychiatric consequences, especially during childhood while the brain development is not finished. When the neurological damage affects the frontal lobes of the brain, behavioural and personality disturbances are expected and an early multidisciplinar intervention should be considered. Antypsichotics are the gold standard pharmacological treatment for behavioural disturbances. During the scholar period, special curricular adaptations should be done in order to reduce study-related stress.Disclosure of InterestNone Declared

It has been reported that bioelectric alterations in an electroencephalogram (EEG) may play an etiological role in neurodevelopmental disorders. The clinical impact of interictal epileptiform discharges (IEDs) in association with autistic spectrum disorder (ASD) is unknown. The Autism Diagnostic Interview-Revised (ADI-R) is one of the gold standards for the diagnosis of autistic spectrum disorder. Some studies have indicated high comorbidity of IED and ASD, while other studies have not supported an association between the central symptoms of autism and IED. This review examines the high comorbidity and clinical impact of IED; patients with epilepsy are excluded from the scope of this review. ASD can be disabling and is diagnosed at an average age of 5 years old, at which point the greatest neurological development has occurred. If an association between IED and ASD is identified, a clinical tool that entails an innocuous procedure could enable diagnosis in the first years of life. However, in the absence of reports that prove an association between IED and ASD, patients should not be subjected to expensive treatments, such as the administration of anticonvulsant therapies.

Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (−32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.

Nanostructured surfaces with embedded noble metal nanoparticles is an attractive way for manipulation with the optical properties of wide bandgap semiconductors applied in optoelectronics, photocatalytic processes or for Surface-Enhanced Raman spectroscopy. Ion implantation offers an effective way for nanoparticle preparation without the use of additional chemicals that offers precise control of nanoparticle depth distribution. The aim of this study is a synthesis of the gold nanoparticles in GaN by implantation of 1.85 MeV Au ions with high fluences up to 7×1016 cm-2 and study of optical properties of Au implanted GaN. Implanted crystals were annealed at 800 °C in an ammonia atmosphere for 20 min to support Au nanoparticle creation and GaN recovery. The structure characterisation has been realized by Rutherford backscattering spectroscopy in channelling mode and it showed the formation of two separated disordered regions – the surface region and buried layer. The lower implantation fluences induce damage mainly in a buried layer; however, the increase of the Au-ion fluence leads to the increase of surface disorder as well. Further, the increase of the Au-ion fluence induces the Au dopant shift to the surface and multimodal Audepth profiles. TEM analyses confirmed the formation of Au nanoparticles in the implanted samples after annealing with sizes up to 14 nm. The increase of light absorption and modification of GaN bandgap of the Au modified GaN was deduced from the change in optical transmission spectra between 370 – 1400 nm.

In this paper, an electrochemical sensor for epinephrine (EP), a neurotransmitter was developed by anchoring molecularly imprinted polymeric matrix (MIP) on the surface of gold-coated quartz crystal electrode of electrochemical quartz crystal microbalance (EQCM) using starch nanoparticles (Starch NP) — reduced graphene oxide (RGO) nanocomposite as polymeric format for the first time. Use of EP in therapeutic treatment requires proper dose and route of administration. Proper follow-up of neurological disorders and timely diagnosis of them has been found to depend on EP level. The MIP sensor was developed by electrodeposition of starch NP-RGO composite on EQCM electrode in presence of template EP. As the imprinted sites are located on the surface, high specific surface area enables good accessibility and high binding affinity to template molecule. Differential pulse voltammetry (DPV) and piezoelectrogravimmetry were used for monitoring binding/release, rebinding of template to imprinted cavities. MIP-coated EQCM electrode were characterized by contact angle measurements, AFM images, piezoelectric responses including viscoelasticity of imprinted films, and other voltammetric measurements including direct (DPV) and indirect (using a redox probe) measurements. Selectivity was assessed by imprinting factor (IF) as high as 3.26 (DPV) and 3.88 (EQCM). Sensor was rigorously checked for selectivity in presence of other structurally close analogues, real matrix (blood plasma), reproducibility, repeatability, etc. Under optimized conditions, the EQCM-MIP sensor showed linear dynamic ranges (1–10[Formula: see text][Formula: see text]M). The limit of detection 40 ppb (DPV) and 290 ppb (EQCM) was achieved without any cross reactivity and matrix effect indicating high sensitivity and selectivity for EP. Hence, an eco-friendly MIP-sensor with high sensitivity and good selectivity was fabricated which could be applied in “real” matrices in a facile manner.

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare, genetically determined neurological disorder, for which Ketogenic Diet (KD) represents the gold standard life-long treatment. The aim of this study is to investigate health related quality of life in a well characterized cohort of patients affected by GLUT1DS treated with KD, evaluating factors that can influence patients’ and parents’ quality of life perception. Methods: This is a double center exploratory research study. A postal survey with auto-administrable questionnaires was conducted among 17 subjects (aged 3–22 years) with diagnosis of GLUT1DS, receiving a stable KD treatment for more than 1 year. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales was adopted. Clinical variables analyzed in relation to quality of life were frequency of epileptic seizures and movement disorder since KD introduction, presence of intellectual disability (ID), and KD ratio. Results: Quality of life global scores were impaired both in parents’ and children’s perspectives, with a significant concordance. Taking into consideration subscales, the average was 64.17 (range 10–100) for physical functioning, 74.23 (range 30–100) for emotional functioning, 62.64 (range 10–100) for social functioning, and 56 (range 15–92) for school functioning. Conclusions: In patients with GLUT1DS the quality of life perception is comparable to that of other patients with chronic disease. In our sample, the presence of movement disorder seems to be a crucial element in quality of life perception.

The central nervous system disorders represent a worldwide public health problem. Neuro-degeneration is associated with many transitions in brain including synaptic disorder and neuro-cognition decline. It is shielded by a barrier which controls the entry of compounds into the brain known as blood brain barrier (BBB), there by regulating brain homeostasis. In achieving a therapeutic amount of drug to the proper site of action in the body and then maintaining the desired amount of drug concentration for a sufficient time interval to be clinically effective for treatment. Particularly, neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) are becoming further established in the elderly inhabitants of the society. These ailments usually encompass advanced degeneration & neuronal loss, rendering these disorders spread and difficult to treat. There are various types of pharmaceutical approaches to treat the neurological disorders. The drug loaded Nano-carriers are one of them. In this review, we will address the different applications of drug loaded Nano-carriers in the treatment of various neurological disorders. The Nano-carriers developed to enhance drug delivery across the BBB include micelles, exosomes, liposomes, nanotubes, nanoparticle, Nano emulsions, dendrimers, Nano gels, and quantum dots, etc. The recent developments in Nano-carriers’ implementation through size/charge optimization and surface modifications like PE Gylation, targeting delivery, and coating with surfactants have been discussed, and a detailed description of the Nano-scaled pharmaceutical delivery devices employed for the treatment of central nervous system disorders has also been defined. This review provides a brief overview of the variety of carriers employed for central nervous system drug and diagnostic probes delivery.

Background: Central nervous system vasculitis (CNSV) is a rare disorder, the pathophysiology of which is not fully understood. It involves a combination of inflammation and thrombosis. CNSV is most commonly associated with headache, gradual changes in mental status, and focal neurological symptoms. Diagnosis requires the effective use of history, laboratory testing, imaging, and biopsy. Catheter angiography can be a powerful tool in the diagnosis when common and low-frequency angiographic manifestations of CNSV are considered. We review these manifestations and their place in the diagnostic algorithm of CNSV. Summary: We reviewed the PubMed database for case series of CNSV that included 5 or more patients. Demographic and angiographic findings were collected. Angiographic findings were dichotomized between common and low-frequency findings. A system for incorporating these findings into clinical decision-making is proposed. Key Message: CNSV is a diagnostic challenge due to the absence of a true gold standard test. In the absence of such a test, catheter angiography remains a central piece of the diagnostic puzzle when appropriately employed and interpreted.

The World Health Organization (WHO) suggests that mental disorders, neurological disorders, and suicide are growing causes of morbidity. Depressive disorders, schizophrenia, bipolar disorder, Alzheimer’s disease, and other dementias account for 1.84%, 0.60%, 0.33%, and 1.00% of total Disability Adjusted Life Years (DALYs). Furthermore, suicide, the 15th leading cause of death worldwide, could be linked to mental disorders. More than 68 computer-aided diagnosis (CAD) methods published in peer-reviewed journals from 2016 to 2021 were analyzed, among which 75% were published in the year 2018 or later. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was adopted to select the relevant studies. In addition to the gold standard, the sample size, neuroimaging techniques or biomarkers, validation frameworks, the classifiers, and the performance indices were analyzed. We further discussed how various performance indices are essential based on the biostatistical and data mining perspective. Moreover, critical information related to the Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines was analyzed. We discussed how balancing the dataset and not using external validation could hinder the generalization of the CAD methods. We provided the list of the critical issues to consider in such studies.

Background. Autism spectrum disorder (ASD) is a chronic developmental disability caused by differences in the brain. The gold standard for the diagnosis of this condition is based on behavioral science, but research on the application of neurological detection to diagnose the atypical nervous system of ASD is ongoing. ASD neuroimaging research involves the examination of the brain’s structure, functional connections, and neurometabolic. However, limited medical resource and the unique heterogeneity of ASD have resulted in many challenges when neuroimaging is utilized. Objective. This bibliometric study is aimed at summarizing themes and trends in research on autism spectrum disorder neuroimaging and at proposing potential directions for future inquiry. Methods. Citations were downloaded from the Web of Science Core Collection database on neuroimaging published from January 1, 2012, to December 31, 2021. The retrieved information was analyzed using Bibliometric.com, CiteSpace.5.8. R3, and VOS viewer. Results. A total of 1,363 papers were published across 58 regions. The United States was the leading source of publications. The League of European Research Universities published the largest number of articles (171). Burst keywords from 2018 to 2021 include identification and network. The clusters of references that continued into 2020 included graph theory, functional connectivity, and classification, which represent key research topics. Conclusions. Imaging data is being used to identify neuro-network models with higher accuracy for ASD discrimination. Functional near-infrared imaging is advantageous compared to other neuroimaging. In the future, research on systematic and accurate computer-aided diagnosis technology should be encouraged. Moreover, the study of neuroimaging of ASD in different psychological and behavioral states can inspire new ideas about the diagnosis and intervention training of ASD and should be explored.

Object Tethered cord syndrome (TCS) is a disorder involving an abnormal stretching of the tethered spinal cord caused by several pathological conditions and presents with a variety of neurological symptoms. Untethering (tethered cord release) is the gold standard treatment for TCS. However, untethering carries risks of spinal cord injury and postoperative retethering. To avoid these potential risks, the authors applied spine-shortening osteotomy to adult patients with TCS, and report on the surgical procedure and treatment outcomes. Methods Eight patients with TCS caused by a lipomyelomeningocele were surgically treated by the authors' original procedure of spine-shortening osteotomy. Six patients were male and 2 were females; average age at the time of surgery was 31 years old. Spine-shortening osteotomy was performed at the level of L-1 in all but 2 patients, in whom it was performed at T-12, with spinal fusion between T-12 and L-2 or T-11 and L-1 using a pedicle screw–rod system. The average follow-up period was 6.2 years and the patients' pre- and postoperative conditions were evaluated clinically and radiologically. Results Preoperatively, all patients displayed severe neurological deficits such as motor disturbance, muscle atrophy, and bladder dysfunction. Several months before surgery, all showed progressive symptoms. Those symptoms showed initial improvement in 6 patients and stabilized in 2 postoperatively, but the improved symptoms worsened again in 4 of the 6 patients. The osteotomized vertebrae were shortened by 21 mm on average, and all spines showed complete bone union without loss of correction. At the final follow-up evaluations, 6 patients showed stabilization as per the modified Japanese Orthopaedic Association score for thoracic myelopathy. Conclusions Spine-shortening osteotomy successfully helps reduce the spinal cord tension without causing direct neural damage. At minimum, it stabilized the patients' symptoms and/or helped delay neurological deterioration for a period of time. Spine-shortening osteotomy might be a feasible mode of treatment for adult TCS caused by a spinal lipoma.

Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO). Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL-) 6 and prostaglandin E2levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-αlevels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

Parkinson’s disease (PD) is a neurodegenerative disorder that is more common in elderly people and affects motor control, flexibility, and how easily patients adapt to their walking environments. PD is progressive in nature, and if undetected and untreated, the symptoms grow worse over time. Fortunately, PD can be detected early using gait features since the loss of motor control results in gait impairment. In general, techniques for capturing gait can be categorized as computer-vision-based or sensor-based. Sensor-based techniques are mostly used in clinical gait analysis and are regarded as the gold standard for PD detection. The main limitation of using sensor-based gait capture is the associated high cost and the technical expertise required for setup. In addition, the subjects’ consciousness of worn sensors and being actively monitored may further impact their motor function. Recent advances in computer vision have enabled the tracking of body parts in videos in a markerless motion capture scenario via human pose estimation (HPE). Although markerless motion capture has been studied in comparison with gold-standard motion-capture techniques, it is yet to be evaluated in the prediction of neurological conditions such as PD. Hence, in this study, we extract PD-discriminative gait features from raw videos of subjects and demonstrate the potential of markerless motion capture for PD prediction. First, we perform HPE on the subjects using AlphaPose. Then, we extract and analyse eight features, from which five features are systematically selected, achieving up to 93% accuracy, 96% precision, and 92% recall in arbitrary views.

Psychogenic nonepileptic seizures (PNES) are a functional neurological disorder/conversion disorder subtype, which are neurobehavioral conditions at the interface of neurology and psychiatry. Significant advancements over the past decade have been made in the diagnosis, management, and neurobiological understanding of PNES. This article reviews published PNES research focusing on semiologic features that distinguish PNES from epileptic seizures, consensus diagnostic criteria, the intersection of PNES and other comorbidities, neurobiological studies, evidence-based treatment interventions, and outcome studies. Epidemiology and healthcare utilization studies highlight a continued unmet medical need in the comprehensive care of PNES. Consensus guidelines for diagnostic certainty are based on clinical history, semiology of witnessed typical event(s), and EEG findings. While certain semiologic features may aid in the diagnosis of PNES, the gold standard remains capturing a typical event on video electroencephalography (EEG) showing the absence of epileptiform activity with history and semiology consistent with PNES. Medical-neurologic and psychiatric comorbidities are prevalent in PNES; these should be assessed in diagnostic evaluations and integrated into treatment interventions and prognostic considerations. Several studies, including a pilot, multicenter, randomized clinical trial, have now demonstrated that a cognitive behavioral therapy–informed psychotherapy is an efficacious treatment for PNES, and additional efforts are necessary to evaluate the utility of pharmacologic and other psychotherapy treatments. Neuroimaging studies, while requiring replication, suggest that PNES may occur in the context of alterations within and across sensorimotor, emotion regulation/processing, cognitive control, and multimodal integration brain systems. Future research could investigate similarities and differences between PNES and other somatic symptom disorders.

Background: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

Background: Complex regional pain syndrome (CRPS) is a chronic pain disorder that develops as a consequence of trauma to one or more limbs. Despite the availability of multiple modalities to diagnose CRPS, a gold standard technique for definitive diagnosis is lacking. Moreover, there are limited reports describing the use of spinal cord stimulation (SCS) to treat CRPS Type II, given the low prevalence of this condition. Herein, we present the case of a patient with CRPS Type II with novel thermography findings who underwent SCS for pain management after an Achilles tendon repair surgery. Case Description: A 38-year-old woman was referred to our institute because of chronic left leg pain after Achilles tendon rupture repair surgery. Her case was diagnosed as CRPS Type II based on the International Association for the Study of Pain diagnostic criteria. After an epidural block, thermography showed a significant increase in the body surface temperature of the foot on the observed side. She was subsequently treated with SCS, following which her pain ameliorated. She reported no pain flare-ups or new neurological deficits over 2 years of postoperative follow-up assessments. Conclusion: SCS could be a useful surgical treatment for medication refractory CRPS Type II as supported by our thermography findings. We may refine surgical indication for permanent implantation of SCS with the presented method.

SVcPACNS is a rare inflammatory/immune disorder that typically affects the small blood vessels of the brain. SVcPACNS differs from most adult forms of PACNS by being predominantly lymphocytic, non-granulomatous and non-necrotizing. Previously healthy children are typically affected by range of signs and symptoms, including: seizures, headache, cognitive decline, behavior/personality change, focal neurological deficits and potentially a decreased level of consciousness. Treatment protocols featuring induction (steroids and cyclophosphamide) and subsequent maintenance phases (e.g., mycophenolate mofetil) have been demonstrated to yield favorable outcomes. Since SVcPACNS is characteristically angiography negative, the diagnostic gold standard is brain biopsy. Interpretation of these biopsies is often challenging given the histologic overlap between SVcPACNS and encephalitis. Distinguishing the foregoing is critical since the treatment of these entities is significantly different.Herein, a rare autopsy case of SVcPACNS in a 4 year old male is presented. This case provides a unique opportunity to review the Alrawi criteria for the histologic diagnosis of PACNS and establish/refine criteria specific to SVcPACNS. Generally, such criteria should feature: 1) an intramural and lymphocyte predominant infiltrate devoid of multinucleated giant cells; 2) structural vessel alterations lacking fibrinoid necrosis; 3) perivascular pathology supportive of an angiocentric process; 4) the absence of encephalitis; and, 5) the absence of a concurrent systemic or rheumatic illness that could account for the CNS findings.

Marchiafava Bignami disease (MBD) is a neurological disorder characterized by myelin degeneration and tissue necrosis within the central nervous system. This condition predominantly afflicts individuals with chronic alcohol abuse and malnutrition. The most distinctive pathological feature of MBD is the necrotic degeneration specifically observed in the corpus callosum; however, emerging evidence also indicates the potential involvement of other brain regions. The main pathophysiological mechanisms involve alcohol consumption, which leads to thiamine depletion and disrupts various metabolic pathways. This, in turn, hinders myelin synthesis and impairs signal transmission, resulting in a wide range of symptoms and signs. MBD can manifest in different stages, including acute, subacute, and chronic, each with varying severity. Diagnosing MBD can be challenging due to its presenting symptoms being nonspecific. In the era preceding the development of sophisticated imaging methodologies, the diagnosis of MBD was primarily established through postmortem examination conducted during autopsies. However, with a detailed medical history and imaging modalities such as magnetic resonance imaging (MRI) and computed tomography (CT), it is now possible to diagnose MBD and differentiate it from other diseases with similar clinical presentations. MRI is considered the gold standard for visualizing lesions in the corpus callosum and other affected areas. Also, positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS) could show brain damage in the corpus callosum associated with MBD. MRI-diffusion-weighted imaging (DWI) detects early lesions, while diffusion tensor imaging (DTI) investigates clinical manifestations and recovery. Poor prognostic indicators for MBD include extensive cerebral cortex involvement and severe disturbances in consciousness. Differential diagnosis involves ruling out other alcohol-related disorders, such as neoplastic conditions, Wernicke's encephalopathy, and multiple sclerosis, among others, through careful evaluation. The therapeutic strategies for the management of MBD are currently lacking definitive establishment; however, available evidence indicates that targeted interventions have the potential to induce amelioration. Corticosteroids offer prospective advantages in addressing brain edema, demyelination, and inflammation; research findings present a heterogeneous outcome pattern. Notably, thiamine treatment reduces the likelihood of unfavorable consequences, particularly when administered promptly, and thus is endorsed as the primary therapeutic approach for MBD. This review will highlight this rare disease that many healthcare providers might not be familiar with. By understanding its clinical presentation, differential diagnosis, imaging, and management, medical providers might better identify and diagnose MBD. Raising awareness about this condition can lead to better prevention, early detection, and timely intervention.

Epilepsy is a neurological disorder involving persistent spontaneous seizures and uncontrolled neuronal excitability that leads to cognitive impairments and blood–brain barrier (BBB) disruption. Currently available antiepileptic drugs present side effects and researchers are trying to discover new agents with properties to overcome these drawbacks. The aim was to synthesize magnesium oxide (MgO) and zinc oxide (ZnO) nanoparticles from Datura alba fresh leaf extracts and evaluate their anti-epileptic potential in mice kindling or a repetitive seizures model. The phytoassisted synthesized nanoparticles were characterized using spectroscopy; FT-IR, XRD, SEM, and EDX. Analysis of the NPs confirmed the crystalline pleomorphic shape using the salts of both zinc and magnesium possibly stabilized, functionalized and reduced by bioactive molecules present in plant extract. By using several characterization techniques, NPs were confirmed. UV-Vis spectroscopy of biologically produced ZnO and MgO revealed distinctive peaks at 380 nm and 242 nm, respectively. Our findings categorically demonstrated the reductive role of biomolecules in the formation of ZnO and MgO NPs. The mice kindling model was induced using seven injections of Pentylenetetrazole (PTZ, 40 mg/kg, i.p) for 15 days alternatively. The results showed that mice post-treated with either ZnO or MgO nanoparticles (10 mg/kg, i.p) significantly improved in respect of behavior and memory as confirmed in the Morris water maze (MWM), open field (OF), novel object recognition (NOR) test compared with PTZ treated mice. Furthermore, the ZnO and MgO nanoparticle treatment also maintained the integrity of the BBB, reducing the leakage, as confirmed by Evans blue dye (EBD) compared with PTZ treated mice only. In summary, the current finding demonstrates that green synthesized ZnO and MgO nanoparticles have neuroprotective, ant-epileptic potential, molecular mechanisms, and clinical implications need to be further explored.

Isolated dystonia is a neurological disorder of heterogeneous pathophysiology, which causes involuntary muscle contractions leading to abnormal movements and postures. Its diagnosis is remarkably challenging due to the absence of a biomarker or gold standard diagnostic test. This leads to a low agreement between clinicians, with up to 50% of cases being misdiagnosed and diagnostic delays extending up to 10.1 y. We developed a deep learning algorithmic platform, DystoniaNet, to automatically identify and validate a microstructural neural network biomarker for dystonia diagnosis from raw structural brain MRIs of 612 subjects, including 392 patients with three different forms of isolated focal dystonia and 220 healthy controls. DystoniaNet identified clusters in corpus callosum, anterior and posterior thalamic radiations, inferior fronto-occipital fasciculus, and inferior temporal and superior orbital gyri as the biomarker components. These regions are known to contribute to abnormal interhemispheric information transfer, heteromodal sensorimotor processing, and executive control of motor commands in dystonia pathophysiology. The DystoniaNet-based biomarker showed an overall accuracy of 98.8% in diagnosing dystonia, with a referral of 3.5% of cases due to diagnostic uncertainty. The diagnostic decision by DystoniaNet was computed in 0.36 s per subject. DystoniaNet significantly outperformed shallow machine-learning algorithms in benchmark comparisons, showing nearly a 20% increase in its diagnostic performance. Importantly, the microstructural neural network biomarker and its DystoniaNet platform showed substantial improvement over the current 34% agreement on dystonia diagnosis between clinicians. The translational potential of this biomarker is in its highly accurate, interpretable, and generalizable performance for enhanced clinical decision-making.

Introduction. Lyme neuroborreliosis is an infectious disorder of the central and/or peripheral nervous system caused by the tick stump of the genus Ixodes rici, infected with species Borrelia burgdorferi sensu lato (in Europe). The disease manifests as meningitis, encephalitis, meningoradiculitis, vasculitis, paresthesia of the facial nerve and painful radiculopathy. Case report. A 44-year-old patient reports fatigue, forgetfulness, headache, confusion, depression, drowsiness, irritability, instability, her undercooks are crushed, sheeps of a bride and does not recall being called an object. Muscular reflexes of the undergrowth are reduced. Plantar response flexion, Lazarevic sign is positive at 45 degrees from the surface. No weakness of the dorsal and plantar flexion of the fingers of the feet. Relieves sensitivity in the region of inertia nerv peroneus and tibialis. Sphincters were fine. The patient had a diagnosed Lyme disease, five months prior to the exacerbation of anxiety. Due to erythema migrans and subfebrility, diagnosis and seropositivity to Borrelia burgdorferi were established in both classes of the enzymelinked immunosorbent assay antibodies and a confirmed Western blot test. She took doxycycline 200 milligrams/day, three weeks. The analysis of cerebrospinal fluid revealed proteinhorn (0.42 g/L), normal glycorrhachia, pleocytosis, and positive intrathecal IgG antibodies. Electromyography pointed to axonal degeneration of the lower extremities. The magnetic resonance is neat. The therapy includes ceftriaxone, 2 grams/day, vitamins and analgesic therapy. Neuroborreliois was maintained by the laboratory during one-year follow-up. Mental disorders, headaches, confusion and irritability, neurological signs have significantly regressed. Conclusion. The gold standard in diagnostics of neuroborelliosis is the determination of intrathecal antibodies. For the definitive diagnosis, clinical signs of disease, pleocytosis and positive antibodies are necessary. Intrathecal antibodies remain long positive and they are not recommended for monitoring for the effects of therapy.

The dichotomy between advanced materials and brain has driven the curiosity of scientists to explore the wonders of the brain, as well as motivated the continued innovations of novel technologies based on advances in materials science and engineering to understand the brain. To improve treatments of brain-related diseases will require new tools and methods to map and to repair the brain with precision and biocompatibility. Current treatments of pain heavily rely on opioids, resulting in significant side effects such as addiction, tolerance, leading to the Opioid Overdose Crisis as we know of today. Smart drug delivery systems may provide an effective solution. Here I present the development of polymer-based externally-triggerable drug delivery systems for on-demand, repeatable and adjustable local anesthesia, where the timing, duration, and intensity of nerve block can be controlled through external energy triggers such as light. In addition to the new pharmacological approaches, bioelectronic platforms to enhance our insights into the eye and will also be discussed. The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, I develop artificial retina based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. My study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices. Through pharmacological, optical, and electrical toolsets, I aim to develop effective therapeutic solutions to neurological disease states. These results, along with a discussion of future neural interfaces, aim to improve our understanding of the nervous system and to inform new therapeutic approaches for biomaterials and bioelectronics.

Background The population is aging on a global scale, triggering vulnerability for chronic multimorbidity, balance disorders, and falls. Falls with injuries are the main cause of accidental death in the elderly population, representing a relevant public health problem. Balance disorder is a major risk factor for falling and represents one of the most frequent reasons for health care demand. The use of information and communication technologies to support distance healthcare (eHealth) represents an opportunity to improve the access and quality of health care services for the elderly. In recent years, several studies have addressed the potential of eHealth devices to assess the balance and risk of falling of elderly people. Remote rehabilitation has also been explored. However, the clinical applicability of these digital solutions for elderly people with balance disorders remains to be studied. Objective The aim of this review was to guide the clinical applicability of eHealth devices in providing the screening, assessment, and treatment of elderly people with balance disorders, but without neurological disease. Methods A systematic review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. Data were obtained through searching the PubMed, Google Scholar, Embase, and SciELO databases. Only randomized controlled trials (RCTs) or quasiexperimental studies (QESs) published between January 2015 and December 2019 were included. The quality of the evidence to respond to the research question was assessed using Joanna Briggs Institute (JBI) Critical Appraisal for RCTs and the JBI Critical Appraisal Checklist for QESs. RCTs were assessed using the Cochrane risk of bias tool. We provide a narrative synthesis of the main outcomes from the included studies. Results Among 1030 unduplicated articles retrieved, 21 articles were included in this review. Twelve studies explored different technology devices to obtain data about balance and risk of falling. Nine studies focused on different types of balance exercise training. A wide range of clinical tests, functional scales, classifications of faller participants, sensor-based tasks, intervention protocols, and follow-up times were used. Only one study described the clinical conditions of the participants. Instrumental tests of the inner ear were neither used as the gold-standard test nor performed in pre and postrehabilitation assessments. Conclusions eHealth has potential for providing additional health care to elderly people with balance disorder and risk of falling. In the included literature, the heterogeneity of populations under study, methodologies, eHealth devices, and time of follow-up did not allow for clear comparison to guide proper clinical applicability. This suggests that more rigorous studies are needed.

Stroke is a cerebrovascular disease, contributing to major morbidity and mortality worldwide, with significant clinical and socioeconomic burdens [1]. In Malaysia, stroke is ranked as the third leading cause of death after ischemic heart disease and pneumonia with an alarming rising trend [2]. There are two major types of strokes, namely ischemic stroke (IS) and haemorrhagic stroke. IS caused by thromboembolic occlusion of cerebral artery is the main type of stroke in Malaysia, in which it is comprised up to two-third of total reported stroke cases, as compared to the haemorrhagic stroke [3]. Main pathological events of brain ischemia include a series of biological reactions such as oxidative stress, inflammatory cytokine release, and ischemic-reperfusion injury, leading to cell apoptosis and irreversible neurological damage [4]. Up to date, recombinant tissue plasminogen activator (rt-PA) is still the gold standard drug approved by Food and Drug Administration (FDA) for the clinical treatment of IS [5]. However, due to its narrow therapeutic window (<4.5h), high re-incidence rate and short half-life (<5 min) [5], the application of rt-PA is limited [6]. Therefore, many researchers are exploring other therapeutic approaches to tackle this disease. In recent years, increasing evidences have discovered the potential of natural compounds extracted from plants as a promising alternative strategy against IS. Among the potential plant that possess blood-brain barrier properties, an important characteristics as neuroprotective agent for neurological disorder is Oroxylum indicum [6]. It has been reported that O. indicum has a dominant active compound, namely as baicalein that are responsible in this plant’s biological activities [7]. Therefore, in this study, we aimed to evaluate the potential of baicalein extracted from the leaves of Oroxylum indicum to treat the diseases. Briefly, 10 male Sprague Dawley rats were used in this study (n=5). 50 mg/kg b.wt of baicalein was orally administered via oral gavage before and after induction of ischemic stroke by endothelin-1 (ET-1), while control group was given normal saline. Assessments of behavioral scoring using modified neurological severity score (mNSS) and infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining were evaluated as the endpoint of this study. Results demonstrated that the oral administration of baicalein improved the behavioral scoring of rats in motor test (forelimb flexion and forelimb twisting), contralateral sensory test (paw-whiskers), motor coordination and balance function and reflex test (pinna, corneal, startle and tail reflex) within 24 h -72 h, indicating that the baicalein-treated rats exhibited faster recovery rate as compared to non-treated rats (Figure 1A-D). Such improvements were observed up to two weeks. In addition, histological assessment using TTC staining also revealed reduction of infarct volume in baicalein-treated rats as compared to control rats. However, the percentage of infarct volume to whole brain was not significantly different in both groups (Figure 2). The promising results displayed by baicalein might be contributed by its anti-inflammatory property. Several studies reported that baicalein, a type of flavonoid compound, are responsible in attenuation of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage and inhibit NF-kB activation [7,8]. LPS is the potent macrophage activator, while NF-kB is a transcription factor that can cause inflammatory cytokines release in various cell types [9, 10]. In summary, the present study demonstrates that oral administration of baicalein in ischemic stroke rats could be effectively addressed and improved behavioral scoring in treated rats as early as 24 h after baicalein treatment.

BACKGROUND Parkinson's disease (PD) is a progressive neurological disorder characterized by symptoms of bradykinesia, tremor, and muscle rigidity. Previous studies have shown that high cadence dynamic cycling promotes significant improvement in PD motor symptoms. This improvement is attributed to a higher entropy (variability) of cadence during dynamic cycling. However, it is not clear how entropy of cadence and level of effort can be utilized to develop individualized exercise prescriptions for individuals with PD, as well as how patient specific adaptive dynamic cycling impacts motor function and mobility in individuals with PD. Therefore, the purpose of this study was to develop an individualized exercise paradigm by manipulating entropy of cadence and level of effort and also examine the effects on motor function and mobility in PD. METHODS/DESIGN 11 individuals diagnosed with idiopathic PD were randomized into either the patient-specific adaptive dynamic cycling (PSADC) or an active control (AC) group. The dynamic cycle resistance settings were optimized for each individual in the PSADC group, while settings remained constant in the AC group. Each group completed 12 sessions over the course of 4 weeks. Motor function and mobility were measured at baseline and after 12 exercise sessions using the clinical and Kinesia One Unified Parkinson's Disease Rating Scale Motor III (UPDRS Motor III) and the Timed Up and Go (TUG). The UPDRS Motor III is the gold standard measurement of PD symptom severity. TUG is a mobility assessment that is highly correlated to overall functional mobility. Outcome measures were compared using repeated measures ANOVA, as well as paired samples and independent samples t-tests. RESULTS Individuals in the PSADC group saw significant improvements UPDRS Motor III score (Pre: 43.33, Post: 36.67; p=0.040), Kinesia One UPDRS Motor III score (Pre: 25.142, Post 23.833; p = 0.017), and TUG completion time (Pre: 12.37s, Post: 9.99s; p=0.036) from baseline to follow up. Individuals in the AC group did not significantly improve motor function (Pre: 28.60, Post: 29.60) or mobility (Pre: 11.23s, Post: 10.85s). CONCLUSIONS PSADC is associated with significant improvements in motor function and mobility in individuals with PD. Future studies will consider developing machine learning or artificial intelligence algorithms to provide accurate and valid exercise prescriptions to be utilized in the clinical rehabilitation for individuals with PD.

Abstract Background Gaucher's disease is a rare autosomal recessive disorder that results from the deficiency of the enzyme glucocerebrosidase, causing deposition of glucocerebroside in cells of the macrophage-monocyte system. Type 3 disease has varied presentations, with neurologic involvement, in addition to progressive hepato-splenomegaly, anemia, thrombocytopenia and skeletal manifestations. Case Report 2 month old infant girl, was noted to have abdominal enlargement, and was taken to the local rural provider. She was referred to a pediatrician. From there, she was transferred to our institution, after a red blood cell transfusion. Past history is noteworthy for early passage of a first degree cousin, at the age of 3 months, with hepatosplenomegaly and transfusion requirements. Parents deny consanguinity. However, they live in a very rural, closed population. A detailed pedigree chart was not obtained. Physical exam revealed an infant in regular overall conditions, grade IV hepatosplenomegaly. Pale, fussy, hyporexic, with mild breathing difficulty, from enlarged abdomen. She had oculomotor apraxia, at the horizontal gaze. Rest of neurological examination was uneventful. Dry blood sample was obtained and sent to a specialized laboratory (Greenwood Genetic Center, USA). Bone marrow biopsy showed almost total replacement of normal hematopoiesis, with Gaucher cells. Beta glucosidase activity was low. GBA gene sequencing, at chromosome 1q21-22, revealed homozygous pL483p mutation, on exon 11. She was 5 months old, when diagnosis of Gaucher's disease type 3, was genetically confirmed. Imiglucerase was initiated, biweekly, at 60 unit/kg. Dose was increased, on a monthly basis, up to 120 unit/kg. Ambroxol was also started, as a chaperone therapy 15mg/kg/d, as per recent literature (Narita et al, Ann Clin Transl Neurol 2016 Feb 2;3(3):200-15), providing increased glucocerebrosidase activity, in the cerebrospinal fluid, with improvement of neurologic symptoms. Blood counts, including platelets, normalized shortly after starting enzyme replacement therapy. Neurologic milestones, growth and constitutional features, are adequate for age. Hepatosplenomegaly has decreased with ongoing therapy, and we expect it will continue to ultimately improve, with treatment. She is now 14 months old. Conclusion Gaucher's disease is a rare condition that should be considered in an infant with hepato-splenomegaly and low blood counts, and or bleeding manifestations. Gold standard for diagnosis should be sought by the enzyme measurement, and molecular confirmation. Enzyme replacement therapy is the therapy of choice, in these patients. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Genetic Addiction Risk Severity (GARS) (Blum et al, 2014; Blum, Badgaiyan, Agan, Frantantonio, Simpatico, et al. 2015; Blum, Baron, Lott, Ponce, Siwicki, et al. 2019) screens for Reward Deficiency Syndrome (RDS) predisposition risk, for polymorphic variance within eleven alleles of the ten most common genes, in mental disorder. The RDS paradigm shift is concerned with treating the underlying neurogenetic and epigenetic challenges of dopaminergic dysfunction, as well as dysfunction in other neurotransmitter channels (Blum, Baron, McLaughlin, & Gold, 2020). Cutting edge psychiatric genomics recognizes that RDS is one preexisting causal influence for addiction (Tsermpini, Adla, & Patrinos, 2022). Consideration of preexisting neurogenetic challenges which affect low dopamine availability or epigenetic insults are not addressed in traditional old school, Minnesota Model twelve steps treatment modalities (Gilley, 2020), nor it is addressed in the current DSM 5th Edition (APA, 2013) (Gondre-Lewis, Bassey, & Blum, 2020). Scientists in the know are hopeful that RDS will be included in the next edition of the Diagnostic and Statistical Manual of Mental Disorders, as exponential increases in research studies from interactive sciences such as psychology, neurology, genetics and epigenetics have greatly enlarged perspective (Mancheno, Navas-Leon, Fernandez-Calderon, Gutierrez, Sanchez-Garcia, et al 2021). Sometimes progress is slow in funneling progressive cutting-edge applications from the research world into the practitioner world (CASA Columbia, 2012). Unfortunately, it is the patients who suffer, as the opioid overdose deaths of more than 100,000 this year alone, attest (Gupta, Bowirrat, Llanos Gomez, Baron, Elman, Giordano, et al 2022; Blum, Fried, Madigan, Giordano, Modestino, Steinbergy, et al 2017; Moran, Blum, Valdez Ponce, Lott, Gondre-Lewis, Badgaiyan, 2021). Not only have there been advancements in treatment models, from the Minnesota Model of the 1950’s, the Harm Reduction Model of the 1980’s (Paquette, Daughters, & Witkiewitz, 2022) and the Neurodevelopmental Model of addiction of the 2000’s (Leyton, 2012, 2014), there have been advancements in unifying theory. The evolution of the history of addiction recovery treatment would never be complete without mentioning the foundational dopamine depletion hypothesis (Dackis, & Gold, 1985; Diani, 2011; Volkow, Fowler, & Wang, 2002), which led to way to the current leading theory of Reward Deficiency Syndrome, which includes consideration of genetic (Dick, & Agrawal, 2008; Uhl, Liu, Walter, Hess, & Naiman, 2002) and epigenetic causal influences (Edwards, Roy, Boyett, Badgaiyan, Thanos, Baron, et al 2020; Vaillancourt, Ernst, Mash, & Turecki, 2017). RDS unifies all addictions, both substance and non-substance under a common rubric (Blum, Bowirrat, Braverman, Baron, Cadet, Kasmi, et al (2021). The Reward Deficiency Syndrome paradigm shift takes into consideration, underlying genetic, biological, physiological, and neurological mechanisms of the brain reward cascade (BRC). In this genomic era of addiction medicine, the new standard of excellence in addiction treatment begins genetic screening (Gilley, 2022 a, b, c). RDS treatment plans are built upon the foundational genetic and epigenetic causal influences (Gilley, 2021, b, c). RDS-Solution Focused Brief Intervention (RDS-SFBI) administers bio-neuro-psychological therapy which assists the client in achieving dopamine homeostasis (Gilley, 2019). Since RDS effects the individual over the entire lifespan, it should be treated as a front-line modality (Blum, Raza, Schultz, Jalali, Green, Brewer, et al 2021), by primary physicians, and teams of RDS specialists (Gilley, Bowirrat, Gupta, Giordano, Dennen, Braverman, Badgaiyan, McLaughin, Baron, & Blum, 2022).

Abstract BACKGROUND: Attention deficit hyperactivity disorder is considered the most common childhoodneurobehavioral disorder worldwide with well documented adverse consequences in adolescence and adulthood, yet 60-80% of cases go undiagnosed. Routinescreening for the condition is not practiced in most pediatric outpatient services andlittle information exists on factors associated with the condition in developingcountries. OBJECTIVES: This was a questionnaire based cross-sectional survey whose primary objective was to determine prevalence of attention deficit hyperactivity disorder (ADHD) symptoms in children aged 6-12 years attending the Accidents and Emergency unit of a tertiary care hospital in Nairobi. Secondary objectives were to (i) ascertain if physical injury and poor academic performance were associated with ADHD, (ii) compare diagnostic utility of parent-filled Vanderbilt Assessment Scale (VAS) against Statistical Manual of Mental Disorders-IV (DSM-IV) as the gold reference and (iii) establish if there exists an association between ADHD symptoms cluster and comorbid conditions. DESIGN/METHODS: The study was undertaken at the paediatric accidents and emergency (A&E) section of the Aga Khan University Hospital (AKUHN) between March and June 2012. AKUHN is a private, not for profit, tertiary health care facility based in Nairobi, Kenya. Paediatrics A&E offers a 24-hour service provided by paediatric residents and senior house officers under the supervision of paediatric registrars. Children aged 6-12 years were enrolled provided guardians demonstrated ability to read and write in English. A written signed informed consent was also required from the primary care provider. Children on methylphenidate, antidepressants or behavioral therapy and those with neurological disorders, hearing and visual impairments or need for emergency care were excluded. Those who consented were clinically evaluated and treated for the ailments that brought them to hospital prior to completion of the self-administered study questionnaire. Sample size was estimated at 240 based on estimated ADHD prevalence of 6% reported by Kashala et al from a neighboring country with similar socio-economic setting as Kenya. Study approval was obtained from the Aga Khan University Hospital Scientific and Ethical Review Committees. Enrolling of children was done after written consent from parents or primary guardians as required by the institutional review board for children under the age of 18 years. It was made clear that recruitment was entirely voluntary and that refusal to participate would not in any way compromise provision of care. Study records were secured in a locked cabinet to safeguard confidentiality. Study was carried out using a two-stage ascertainment procedure. Children were evaluated for eligibility after registration at the reception between 9am to 8pm during week days. A maximum of 10 participants were recruited on any given day to minimize burden in the department and to hopefully capture a wider spectrum of medical conditions. Details about the study were explained to the parents by the principal investigator or the research assistant after patients had been seen by the clinician for the presenting problem. Information necessary for DSM-IV classification was obtained from parents who also completed VAS form. Care providers of study children were requested to complete the risk assessment form with assistance provided as needed. It contained questions about school performance such as repetition of class and average end of term marks which was categorized as; below 25%, 25-50%, 50-75% or above 75%. A grade above 50% was considered as acceptable performance. Only injuries for which medical treatment was sought were considered for inclusion and categorized into burns,fractures and open wounds. Information on causes of injuries was classified under falls, fight, car accident and others. Completion of an assessment form took approximately 15 minutes after which questionnaire was scored and tabulated before providing feedback to parents. Data were entered in Microsoft Excel® and analysis done using STATA®Version 11 (StataCorp). Prevalence of ADHD symptoms was calculated using the number of positive cases as numerator and study population as denominator. Chi square or Fischer’s exact test were used as appropriate to compare categorical variables with P-value below 0.05 considered significant. Wilcoxon test was used for ordinal data. Odds ratios (OR) were used to determine association between ADHD symptoms and categorical variables and 95% confidence interval (CI) to determine precision around individual estimates. RESULTS: Prevalence of cluster of symptoms consistent with ADHD was 6.3% (95% CI; 3.72-10.33) in 240 children studied. Those affected were more likely to repeat classes than the asymptomatic (OR 20.2; 95%CI 4.02-100.43). Additionally, 67% of the symptomatic had previously experienced burns and 37% post-traumatic open wounds. The odds of having an injury in the symptomatic was 2.9 (95%CI; 1.01-8.42) compared to the asymptomatic. Using DSM-IV as the reference, VAS had a low sensitivity of 66.7% (95%; CI 39.03-87.12) but specificity of 99.0% (95%CI; 96.1-99.2). Its positive predictive value was 83.0% (95%CI; 50.4-97.3) and the negative predictive value 98.0% (CI 95.1-99.1). Positive and negative likelihood ratios were 75(95%CI; 18.3-311.2) and 0.3 (95%; CI 0.21-0.73) respectively. Oppositional defiant disorder symptoms, anxiety, depression and conduct problems were not significantly associated with ADHD cluster of symptoms. CONCLUSION: A relatively high prevalence of symptoms associated with ADHD was found inchildren visiting the Paediatric Accidents and Emergency department. Symptomaticchildren had also experienced more poor school performance. These findings makea strong case for introduction of a policy on routine screening for ADHD in pediatricoutpatient service in a similar setting. Positive history of injury, especially burns, and poor academic performance is associated with symptoms of ADHD which should trigger need forfurther evaluation for ADHD and appropriate referral. Even though easier toadminister than DSM-IV, Vanderbilt assessment scale has low sensitivity hence itwould not be appropriate for use in ADHD screening. However, in view of its highspecificity and ease of administration, it could be used as an alternative confirmatorytest to determine who among clinically symptomatic patients would require referral to a psychiatrist for further evaluation and management.

Abstract Three topics affecting cobalamin, folate, and homocysteine that have generated interest, activity, and advances in recent years are discussed. These are: (I) the application of an expanded variety of tools to the diagnosis of cobalamin deficiency, and how these affect and are affected by our current understanding of deficiency; (II) the nature of the interaction between homocysteine and vascular disease, and how the relationship is affected by vitamins; and (III) the improved understanding of relevant genetic disorders and common genetic polymorphisms, and how these interact with environmental influences. The diagnostic approach to cobalamin deficiency now allows better diagnosis of difficult and atypical cases and more confident rejection of the diagnosis when deficiency does not exist. However, the process has also become a complex and sometimes vexing undertaking. Part of the difficulty derives from the lack of a diagnostic gold standard among the many available tests, part from the overwhelming numerical preponderance of patients with subclinical deficiency (in which isolated biochemical findings exist without clinical signs or symptoms) among the cobalamin deficiency states, and part from the decreased availability of reliable tests to identify the causes of a patient’s cobalamin deficiency and thus a growing deemphasis of that important part of the diagnostic process. In Section I, Dr. Carmel discusses the tests, the diagnostic issues, and possible approaches to the clinical evaluation. It is suggested no single algorithm fits all cases, some of which require more biochemical proof than others, and that differentiating between subclinical and clinical deficiency, despite their overlap, may be a helpful and practical point of departure in the evaluation of patients encountered in clinical practice. The arguments for and against a suggested expansion of the cobalamin reference range are also weighed. The epidemiologic data suggest that homocysteine elevation is a risk factor for vascular and thrombotic disease. In Section II, Dr. Green notes that the interactions of metabolism and clinical risk are not well understood and a causative relationship remains unproven despite new reports that lowering homocysteine levels may reduce vascular complications. Genetic and acquired influences may interact in important ways that are still being sorted out. The use of vitamins, especially folate, often reduces homocysteine levels but also carries potential disadvantages and even risks. Folate fortification of the diet and supplement use have also markedly reduced the frequency of folate deficiency, and cobalamin deficiency is now the more common deficiency state, especially among the elderly. Although genetic disorders are rare, they illuminate important metabolic mechanisms and pose diagnostic challenges, especially when clinical presentation occurs later in life. In Section III, Drs. Rosenblatt and Watkins use selected disorders to illustrate the subject. Imerslund-Gräsbeck syndrome, a hereditary disorder of cobalamin absorption at the ileal level, demonstrates genetic heterogeneity. Finnish patients show mutation of the gene for cubilin, the multiligand receptor for intrinsic factor. Surprisingly, Norwegian and other patients have been found recently to have mutations of the AMN (amnionless) gene, mutations that are lethal in mice at the embryonic stage. Two disorders of cobalamin metabolism, cblG and cblE, are now known to arise from mutations of the methionine synthase and methionine synthase reductase genes, respectively. These disorders feature megaloblastic anemia and neurologic manifestations. The folate disorder selected for illustration, methylenetetrahydrofolate reductase (MTHFR) deficiency, paradoxically causes neurological problems but no megaloblastic anemia. This rare deficiency is the most common inborn error of folate metabolism. It is distinct from the very common MTHFR gene polymorphisms, mutations that cause mild to moderate reductions in MTHFR activity but no direct clinical manifestations. The MTHFR polymorphisms, especially the 677C→T mutation, may contribute to vascular and birth defect risks, while reducing the risk of certain malignancies, such as colon cancer. These polymorphisms and those of genes for other enzymes and proteins related to cobalamin, folate, and homocysteine metabolism may be important role players in frequent interactions between genes and the environment.

Stroke is a neurological disorder known to be the third leading cause of death in Malaysia. Eighty percent of the cases occurred due to abrupt blockage of blood supply to the brain causing the affected brain area to become damaged and lead to disability or even death [1]. The gold standard treatment via tissue plasminogen activator, however, is most effective to be administered within three hours after the onset of stroke symptoms [2]. According to previous report in 2020, most of the stroke patients that arrived late at the emergency medical care unit were due to the delay in deciding to seek medical attention following the stroke symptoms [3]. Lack of knowledge about the stroke risk factor, signs, and symptoms as well as the tendency of procrastination can result in delay in seeking medical treatment. Several studies had reported the poor level of understanding as well as awareness of stroke signs and symptoms among urban population in Malaysia [4,5]. Therefore, the objective of this cross-sectional study is to explore the awareness and action towards stroke symptoms and risk factors amongst rural population in Selangor, Malaysia. A cross- sectional questionnaire-based study via snowball sampling was conducted amongst the adult individuals residing in several districts of Hulu Selangor, Sabak Bernam and Kuala Selangor that are recognized as rural areas by the Selangor state council. The study used a set of developed questionnaires that consists of two sections: sociodemographic characteristics as well as the awareness and action towards stroke symptoms and risk factors. Descriptive analysis was used to express the variables. Of the 343 respondents, the mean ±SD for awareness on stroke symptoms was 3.9±1.82 out of a total score of 8 whereas awareness on stroke risk factors was 8.9±3.68 out of a total score of 13 (Table 1). The awareness about the stroke symptoms was considered poor as only 36.44% subjects were able to identify all five symptoms of stroke. Meanwhile only 32.4% of respondents were aware of all the risk factors for stroke despite all of them (100%) had heard about stroke. Although most of the respondents recognized stroke as an emergency condition, only 31.8% of them were aware of the appropriate action of calling an ambulance upon recognizing stroke symptoms (Table 2). Previous reports on awareness of stroke symptoms and risk factors were mostly conducted among urban population is Selangor. In 2014, a similar survey conducted among residents in Kajang reported that only 35% of the respondents had satisfactory knowledge of the stroke warning signs while 29% had satisfactory knowledge on the stroke risk factors. Although 78% can correctly recall Emergency Medical Systems number, only 11% were aware of calling the ambulance as the most appropriate action towards witnessing stroke symptoms in individuals [4]. On the other hand, a more recent study conducted among Petaling Jaya residents in 2019 reported that 82.9% to 92.1% of the respondents were able to recognize common symptoms of stroke followed by 74.2% of the study respondents saying that they would go to hospital within 4.5 hours of stroke onset [5]. On contrary, the present study indicates a poor awareness and action towards stroke symptoms amongst rural population in Selangor. Thus, it is suggested that future intervention programs should focus on health promotion and awareness program related to cardiovascular diseases to the community living in the rural districts of Selangor.

Abstract Introduction: Central nervous system involvement (CNSI) in hematologic malignancies confers poor prognosis and is difficult to diagnose requiring clinical, radiological and cytological correlates. Neuroimaging studies generally lack specificity and sensitivity, and although cerebral spinal fluid (CSF) cytology is considered the gold standard, it has a very low sensitivity. Several CSF proteins have been studied as possible biomarkers for CNSI to no avail. CSF levels of beta-amyloid peptides (Ab42) and the proteins S100B, Tau, 14-3-3 and Hexosaminidase B are known to be altered by neurodegenerative disease or neuronal injury. Tau levels have also been shown to increase after intrathecal chemotherapy (ITC) in children with lymphoid malignancies. Because of the absence of a reliable biomarker for CNSI, we initiated a study of patients’ CSF to screen for candidate markers of neuronal damage or inflammation. Materials and Methods: Fifty-eight adult patients with hematological malignancies (31 high-grade non-Hodgkin’s lymphoma, 22 acute lymphoblastic leukemia, 1 post-transplant lymphoproliferative disorder, 2 chronic myelogenous leukemia in accelerated phase, and 2 acute myelogenous leukemia) and 6 normal control patients undergoing spinal anaesthesia were included. CSF samples were obtained and frozen at −80°C until analysis. For patients receiving ITC, the CSF sample was withdrawn prior to ITC administration. Clinical information collected included: age, sex, diagnosis, CNS irradiation, ITC/systemic chemotherapy, and presence or absence of CNS disease. Suspected CNS disease was defined as the presence of focal neurological signs or symptoms consistent with leptomeningeal or parenchymal disease, or radiographic evidence of CNSI. Proven CNS disease was defined by the finding of malignant cells in the CSF by cytology or flow cytometry. The control population consisted of patients undergoing spinal anaesthesia with no clinical or pathologic evidence of hematological malignancy or CNS disease. Tau, S100B and Ab42 were quantified by ELISA. 14-3-3 was assayed by Western blotting. Hexosaminidase B was assayed using a fluorogenic substrate. Variables potentially influencing the levels or presence of markers were explored using Mann-Whitney U tests, Student’s t-test, simple linear regression, ANOVA or Pearson ?2 tests, as appropriate. To test correlation with CNSI multiple logistic regression models were constructed. Receiver operating characteristic (ROC) curves and test performance statistics were generated when feasible. Results: One hundred and twenty-eight samples were analyzed from 58 patients and 6 controls. Whereas no difference was observed for S100B or Ab42, increased levels of Tau or positivity for 14-3-3 were associated with diagnosis, CNSI and probably radiotherapy or ITC (Table 1). Multivariate analysis showed that Tau level or 14-3-3 positivity were associated with CNSI after adjusting for confounders (Table 2). For Tau the area under the ROC curve was 0.791. Sensitivity and specificity were 90 and 33% for a cut-off of 200 pg/mL, and 63% and 90% for a cut-off of 500 pg/ml, respectively. Conclusions: Our results suggest that elevated CSF Tau levels and 14-3-3 positivity may correlate with CNSI in patients with hematologic malignancies and might be useful for diagnosis in suspected cases. These findings warrant further prospective studies. Table 1: Univariate analysis exploring variables potentially influencing Tau levels or presence of 14-3-3 protein P value (2 tailed) for differences in Tau levels P value (2-tailed) for differences in expression of 14-3-3 protein Age 0.992 0.792 Sex 0.372 0.715 Systemic chemotherapy 0.485 0.588 Intrathecal Chemotherapy 0.084 0.191 CNS Radiotherapy 0.163 0.022 Diagnosis &lt;0.001 &lt;0.001 Suspected/confirmed CNS infiltration &lt;0.001 &lt;0.001 Table 2. Logistic regression models exploring CNSI with CSF markers Tau level (Per decile increase) 14-3-3 (Positivity) OR (95% CI) P OR (95% CI) P Unadjusted 1.51 (1.29–1.78) &lt;0.001 7.23 (3.12,–16.76) &lt;0.001 Adjusted for CNS radiotherapy and diagnosis 1.40 (1.17–1.68) &lt;0.001 3.85 (1.48–9.99) 0.006

Abstract Lesions of the central nervous system (CNS) were seen during and after treatment of leukemia. We aimed to characterize the specific pathology and MRI findings observed in leukemia patients with CNS lesions and to determine their value in the management of such patients. The data from stereotactic biopsy for pathology (12 patients) and MRI examinations (14 patients) were retrospectively evaluated. Factors that predisposed to the lesions of CNS were reviewed from the medical records. Among the 14 patients, 4 had a CNS infection, 2 had a neurodegenerative disorder, 8 had CNS leukemia. The clinical diagnosis based on clinical presentation and MRI features was not consistent with the pathological diagnosis in 2 patients: in one patient, the clinical diagnosis was a CNS infection, though the patient's pathological diagnosis was CNS leukemia; in the other patient, the clinical diagnosis was CNS leukemia, but the pathological diagnosis was glial cell hyperplasia. CNS lesions in leukemia have a wide range of causes. Apart from the relapse of leukemia in CNS, there are treatment related neurotoxicities and infections that are caused by immunocompromised states. Stereotactic biopsy for pathological confirmation has the advantages of minimal invasion and convenience, which remains the gold standard for diagnosing the nature of CNS lesions. Because many CNS lesions of leukemia are treatable, early correctly diagnosis is essential. Table 1. Medical records of 14 leukemia patients with CNS lesions case Age, y /Sex Leukemia type A/I* Clinical presentation MRI findings clinical diagnosis Stereotactic biopsy for pathology diagnosis Outcome 1 15/M AML (M5) 14/3 d after Cyclosporin Seizure MRI: The left occipital lobe, right frontal lobe low-density lesions with enhancement of capsule wall. Infection Fungal brain abscesses Improved 2 38/M AML 34/9 mo after allo-HSCT Fever MRI: Scattered lesions at the right frontal lobe. Short T1, long T2 signal. Infection Not performed Improved 3 20/M ALL 20/during 2nd course of chemo Headache, limb tic MRI: Bilateral cerebral hemisphere cortex multiple long T1 and T2 signal nodular lesions. Infection Fungal brain abscesses Improved 4 54/M APL 53/2 mo after Retinoic acid Headache, limb numb, seizure MRI: Bilateral posterior parietal lobe showing patchy enhancement. Leukemia Leukemia Improved 5 7/M ALL (B cell) 7/during the chemo Headache MRI: a cystic lesion in the right temporal lobe and cerebellum obvious edema. Infection Leukemia Progressed 6 26/F AML (M4) 25/during 4th course of chemo Fever, tic MRI: Mixed signals at the left frontotemporal top border zone. Infection Brain abscesses Improved 7 25/M ALL (T cell) 21/3 y after immuno-suppressive agent Headache, limb weakness MRI: Mixed signals at right hemisphere, perilesional mild enhancement. Leukemia T cell leukemia/lymphoma Improved 8 16/M ALL (T cell) 16/ at the diagnosis of leukemia Headache, blurred vision MRI: Scattered, abnormal signal of sizes at the cerebellum. Leukemia Not performed Progressed 9 49/M ALL (B cell) 49/1 mo after chemo none MRI: Glial cell proliferation around lesion at right parietal lobe. Leukemia Glial cell hyperplasia Improved 10 60/M CMML 57/4 y after allo-HSCT Nausea, right limb weakness MRI: a 2.5×2 cm2 lesion in left basal ganglia. Leukemia Chronic myelomonocytic leukemia Died 11 26/M ALL (B cell) 20/9 mo after last course of chemo Headache MRI: lesions at the left temporal lobe, perilesional with obvious edema. Leukemia B cell leukemia/lymphoma Improved 12 29/F AML (M5b) 27/1 mo after last course of chemo none MRI: Bilateral cerebellum, left occipital lobe abnormal signal enhanced on T1 with Gd. Leukemia Leukemia Improved 13 42/M ALL 41/3 mo after allo-HSCT Dizziness, Walking instability MRI: The left cerebellar hemisphere visible nodular enhancement lesions. Leukemia Leukemia Improved 14 23/F ALL (B cell) 23/1 mo after allo-ASCT headache MRI: The right paracele white matter lesions visible long T1, long T2 signal, the boundary is not clear, edema is not obvious, no enhancemen. Degenerative disease Nerve cell degeneration Improved *A, the age when the diagnosis was made for leukemia.I, the interval between the last treatment and the onset of neurological symptoms. Figure 1. The MRI, biopsy site and pathology of a 60-year-old man with CMML Figure 1. The MRI, biopsy site and pathology of a 60-year-old man with CMML Figure 2. The MRI, biopsy site and pathology of a 23-year-old woman with ALL Figure 2. The MRI, biopsy site and pathology of a 23-year-old woman with ALL Figure 3. The MRI, biopsy material and pathology of a 15-year-old man with AML (M5) Figure 3. The MRI, biopsy material and pathology of a 15-year-old man with AML (M5) Disclosures No relevant conflicts of interest to declare.

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. Available at: https://covid19.who.int/ [Accessed on 23 August 2020] Sim K, Chua HC. The psychological impact of SARS: a matter of heart and mind. CMAJ. 2004; 170:811e2. https://doi.org/10.1503/cmaj.1032003. Wu P, Fang Y, Guan Z, Fan B, Kong J, Yao Z, et al. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatr. 2009; 54:302e11. https://doi.org/10.1177/070674370905400504. Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020; 395:912e20. https://doi.org/10.1016/S0140-6736(20)30460-8. Robertson E, Hershenfield K, Grace SL, Stewart DE. The psychosocial effects of being quarantined following exposure to SARS: a qualitative study of Toronto health care workers. Can J Psychiatr. 2004; 49:403e7. https://doi.org/10.1177/070674370404900612. Barbisch D, Koenig KL, Shih FY. Is there a case for quarantine? Perspectives from SARS to Ebola. Disaster Med Public Health Prep. 2015; 9:547e53. https://doi.org/10.1017/dmp.2015.38. Jeong H, Yim HW, Song YJ, Ki M, Min JA, Cho J, et al. Mental health status of people isolated due to Middle East Respiratory Syndrome. Epidemiol Health. 2016;38: e2016048. https://doi.org/10.4178/epih.e2016048. Liu X, Kakade M, Fuller CJ, Fan B, Fang Y, Kong J, et al. Depression after exposure to stressful events: lessons learned from the severe acute respiratory syndrome epidemic. Compr Psychiatr. 2012; 53:15e23. https://doi.org/10.1016/j.comppsych.2011.02.003 Chadda RK, Deb KS. Indian family systems, collectivistic society and psychotherapy. Indian J Psychiatry. 2013;55: S299‑ https://dx.doi.org/10.4103%2F0019-5545.105555. Grover S, Sahoo S, Mehra A, Avasthi A, Tripathi A, Subramanyan A, et al. Psychological impact of COVID‑19 lockdown: An online survey from India. Indian J Psychiatry. 2020; 62:354-62. https://doi.org/ 10.4103/psychiatry.IndianJPsychiatry _427_20. Hawkley LC, Cacioppo JT. Loneliness matters: a theoretical and empirical review of consequences and mechanisms. Ann Behav Med. 2010; 40: 218–27. https://dx.doi.org/10.1007%2Fs12160-010-9210-8. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. https://doi.org/10.1016/S0140-6736(20)30211-7. Bhandari S, Sharma R, Singh Shaktawat A, Banerjee S, Patel B, Tak A, et al. COVID-19 related mortality profile at a tertiary care centre: a descriptive study. Scr Med. 2020;51(2):69-73. https://doi.org/10.5937/scriptamed51-27126. Baumeister RF, Leary MR. The need to belong: desire for interpersonal attachments as a fundamental human motivation. Psychol Bull. 1995; 117: 497–529. https://doi.org/10.1037/0033-2909.117.3.497. Caspi A, Harrington H, Moffitt TE, Milne BJ, Poulton R. Socially isolated children 20 years later: risk of cardiovascular disease. Arch Pediatr Adolesc Med. 2006; 160(8):805-11. https://doi.org/10.1001/archpedi.160.8.805. Eaker ED, Pinsky J, Castelli WP. Myocardial infarction and coronary death among women: psychosocial predictors from a 20-year follow-up of women in the Framingham Study. Am J Epidemiol. 1992; 135(8):854-64. https://doi.org/10.1093/oxfordjournals.aje.a116381. Luo Y, Hawkley LC, Waite LJ, Cacioppo JT. Loneliness, health, and mortality in old age: a national longitudinal study. Soc Sci Med. 2012 Mar; 74(6):907-14. https://dx.doi.org/10.1016%2Fj.socscimed.2011.11.028. Olsen RB, Olsen J, Gunner-Svensson F, Waldstrøm B. Social networks and longevity. A 14-year follow-up study among elderly in Denmark. Soc Sci Med. 1991; 33(10):1189-95. https://doi.org/10.1016/0277-9536(91)90235-5. Patterson AC, Veenstra G. Loneliness and risk of mortality: a longitudinal investigation in Alameda County, California. Soc Sci Med. 2010; 71(1):181-6. https://doi.org/10.1016/j.socscimed.2010.03.024. Savikko N, Routassalo P, Tilvis RS, Strandberg TE, Pitkalla KH. Predictors and subjective causes of loneliness in an aged population. Arch Gerontol Geriatrics. 2005; 41:3;223-33. https://doi.org/10.1016/j.archger.2005.03.002. Health Advisory for Elderly Population of India during COVID19. Available at: https://www.mohfw.gov.in/pdf/AdvisoryforElderlyPopulation.pdf [Accessed on 13 August 2020]. Dicks D, Myers R, Kling A. Uncus and amygdala lesions: effects on social behavior in the free-ranging rhesus monkey. Science. 1969; 165:69–71. https://doi.org/10.1126/science.165.3888.69. Kanai R, Bahrami B, Duchaine B, Janik A, Banissy MJ, Rees G. Brain structure links loneliness to social perception. Curr Biol. 2012; 22(20):1975-9. https://dx.doi.org/10.1016%2Fj.cub.2012.08.045. Bender AR, Daugherty A, Raz N. Vascular risk moderates associations between hippocampal subfield volumes and memory. J Cogn Neurosci. 2013; 25:1851–62. https://doi.org/10.1162/jocn_a_00435. Raz N. Diabetes: brain, mind, insulin–what is normal and do we need to know? Nat Rev Endocrinol. 2011; 7:636–7. https://doi.org/10.1038/nrendo.2011.149. Colcombe SJ, Erickson KI, Naftali R, Andrew GW, Cohen NJ, McAuley E, et al. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci. 2003; 58:176–80. https://doi.org/10.1093/gerona/58.2.m176. Maass A, Düzel S, Goerke M, Becke A, Sobieray U, Neumann K, et al. Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry. 2015; 20, 585–93. https://doi.org/10.1038/mp.2014.114. Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, et al. Loneliness and Risk of Alzheimer Disease. Arch Gen Psychiatry. 2007;64(2):234–240. https://doi.org/10.1001/archpsyc.64.2.234. Kogan JH, Frankland PW, Silva AJ. Long-term memory underlying hippocampus-dependent social recognition in mice. Hippocampus. 2000;10(1):47-56. https://doi.org/10.1002/(sici)1098-1063(2000)10:1%3C47::aid-hipo5%3E3.0.co;2-6. Yorgason JT, España RA, Konstantopoulos JK, Weiner JL, Jones SR. Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats. Eur J Neurosci. 2013;37(6):1022-31. https://doi.org/10.1111/ejn.12113. Bledsoe AC, Oliver KM, Scholl JL, Forster GL. Anxiety states induced by post-weaning social isolation are mediated by CRF receptors in the dorsal raphe nucleus. Brain Res Bull. 2011;85(3-4):117-22. https://dx.doi.org/10.1016%2Fj.brainresbull.2011.03.003. Lukkes JL, Engelman GH, Zelin NS, Hale MW, Lowry CA. Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems. Brain Res. 2012; 1443:1-17. https://dx.doi.org/10.1016%2Fj.brainres.2012.01.005. Ago Y, Araki R, Tanaka T, Sasaga A, Nishiyama S, Takuma K, et al. Role of social encounter-induced activation of prefrontal serotonergic systems in the abnormal behaviors of isolation-reared mice. Neuropsychopharmacology. 2013; 38(8):1535-47. https://doi.org/10.1038/npp.2013.52. Veenema AH. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models? Front Neuroendocrinol. 2009;30(4):497-518. https://doi.org/10.1016/j.yfrne.2009.03.003. Zhao X, Sun L, Jia H, Meng Q, Wu S, Li N, et al. Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(7):1173-1177. https://doi.org/10.1016/j.pnpbp.2009.06.016. Sciolino NR, Bortolato M, Eisenstein SA, Fu J, Oveisi F, Hohmann AG, et al. Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats. Neuroscience. 2010;168(2):371-86. https://dx.doi.org/10.1016%2Fj.neuroscience.2010.04.007. Ghasemi M, Phillips C, Trillo L, De Miguel Z, Das D, Salehi A. The role of NMDA receptors in the pathophysiology and treatment of mood disorders. Neurosci Biobehav Rev. 2014; 47:336-358. https://doi.org/10.1016/j.neubiorev.2014.08.017. Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Fernández AP, Rodrigo J, et al. Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem. 2000;74(2):785-791. https://doi.org/10.1046/j.1471-4159.2000.740785.x. Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008;63(4):349-352. https://doi.org/10.1016/j.biopsych.2007.05.028. Kalia LV, Kalia SK, Salter MW. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol. 2008;7(8):742-755. https://dx.doi.org/10.1016%2FS1474-4422(08)70165-0. Waxman EA, Lynch DR. N-methyl-D-aspartate Receptor Subtypes: Multiple Roles in Excitotoxicity and Neurological Disease. The Neuroscientist. 2005; 11(1), 37–49. https://doi.org/10.1177/1073858404269012. Hermes G, Li N, Duman C, Duman R. Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiol Behav. 2011;104(2):354-9. https://dx.doi.org/10.1016%2Fj.physbeh.2010.12.019. Sestito RS, Trindade LB, de Souza RG, Kerbauy LN, Iyomasa MM, Rosa ML. Effect of isolation rearing on the expression of AMPA glutamate receptors in the hippocampal formation. J Psychopharmacol. 2011;25(12):1720-1729. https://doi.org/10.1177/0269881110385595. Toua C, Brand L, Möller M, Emsley RA, Harvey BH. The effects of sub-chronic clozapine and haloperidol administration on isolation rearing induced changes in frontal cortical N-methyl-D-aspartate and D1 receptor binding in rats. Neuroscience. 2010;165(2):492-499. https://doi.org/10.1016/j.neuroscience.2009.10.039. Alò R, Avolio E, Mele M, Storino F, Canonaco A, Carelli A et al. Excitatory/inhibitory equilibrium of the central amygdala nucleus gates anti-depressive and anxiolytic states in the hamster. Pharmacol Biochem Behav. 2014; 118:79-86. https://doi.org/10.1016/j.pbb.2014.01.007. St JP, Petkov VV. Changes in 5-HT1 receptors in different brain structures of rats with isolation syndrome. General pharmacology. 1990;21(2):223-5. https://doi.org/10.1016/0306-3623(90)90905-2. Miachon S, Rochet T, Mathian B, Barbagli B, Claustrat B. Long-term isolation of Wistar rats alters brain monoamine turnover, blood corticosterone, and ACTH. Brain Res Bull. 1993;32(6):611-614. https://doi.org/10.1016/0361-9230(93)90162-5. Van den Berg CL, Van Ree JM, Spruijt BM, Kitchen I. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies. Eur J Neurosci. 1999;11(9):3023-3032. https://doi.org/10.1046/j.1460-9568.1999.00717.x. Vanderschuren LJ, Stein EA, Wiegant VM, Van Ree JM. Social play alters regional brain opioid receptor binding in juvenile rats. Brain Res. 1995;680(1-2):148-156. https://doi.org/10.1016/0006-8993(95)00256-p. Moles A, Kieffer BL, D'Amato FR. Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science. 2004;304(5679):1983-1986. https://doi.org/10.1126/science.1095943. Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG. Endogenous opioids and social behavior. Neurosci Biobehav Rev. 1980;4(4):473-487. https://doi.org/10.1016/0149-7634(80)90036-6. Gong JP, Onaivi ES, Ishiguro H, Liu Q, Tagliaferro PA, Brusco A, et al. Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res. 2006;1071(1):10-23. https://doi.org/10.1016/j.brainres.2005.11.035. Breivogel CS, Sim-Selley LJ. Basic neuroanatomy and neuropharmacology of cannabinoids. Int Rev Psychiatry 2009; 21:2:113-121. https://doi.org/10.1080/09540260902782760. Haj-Mirzaian A, Amini-Khoei H, Haj-Mirzaian A, Amiri S, Ghesmati M, Zahir M, et al. Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress. Brain Res Bull. 2017; 130:200-210. https://doi.org/10.1016/j.brainresbull.2017.01.018. Banach M, Piskorska B, Czuczwar SJ, Borowicz KK. Nitric Oxide, Epileptic Seizures, and Action of Antiepileptic Drugs. CNS & Neurological Disorders - Drug Targets 2011;10: 808. https://doi.org/10.2174/187152711798072347. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829-37, 837a-837d. https://dx.doi.org/10.1093%2Feurheartj%2Fehr304. Hu Y, Wu D, Luo C, Zhu L, Zhang J, Wu H, et al. Hippocampal nitric oxide contributes to sex difference in affective behaviors. PNAS. 2012, 109 (35) 14224-14229. https://doi.org/10.1073/pnas.1207461109. Khan MI, Ostadhadi S, Zolfaghari S, Mehr SE, Hassanzadeh G, Dehpour, A et al. The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test. Neuroscience Letters. 2016; 612:52-61. https://doi.org/10.1016/j.neulet.2015.12.006. Matsumoto K, Puia G, Dong E, Pinna G. GABAA receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: Possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders. Stress. 2007; 10:1:3-12. https://doi.org/10.1080/10253890701200997. Zlatković J, Filipović D. Chronic social isolation induces NF-κB activation and upregulation of iNOS protein expression in rat prefrontal cortex. Neurochem Int. 2013;63(3):172-179. https://doi.org/10.1016/j.neuint.2013.06.002. Haj-Mirzaian A, Amiri S, Kordjazy N, Momeny M, Razmi A, Balaei MR, et al. Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function. Neuroscience. 2016; 315:271-285. https://doi.org/10.1016/j.neuroscience.2015.12.024. Larson HJ. The biggest pandemic risk? Viral misinformation. Nature 2018; 562:309. https://doi.org/10.1038/d41586-018-07034-4. Zarocostas J. How to fight an infodemic. Lancet 2020; 395:676. https://doi.org/10.1016/S0140-6736(20)30461-X. World Health Organization, 2019. Ebola Virus Disease – Democratic Republic of the Congo. Geneva, Switzerland: WHO. Available at: https://www.who.int/csr/don/28-november-2019-ebola-drc/en/ [Accessed on August 8, 2020] Times of India. Covid-19: doctors gone to collect samples attacked in Indore. Available at: https://timesofindia.indiatimes.com/videos/news/covid-19-doctors-goneto- collect-samples-attacked-in-indore/videoshow/74942153.cms; 2020 [Accessed on August 8, 2020]. Withnall A. Coronavirus: why India has had to pass new law against attacks on healthcare workers. The Independent. April 23, 2020. Semple K. “Afraid to be a nurse”: health workers under attack. The New York Times. 2020 Apr 27. The Economist. Health workers become unexpected targets during COVID-19. The Economist. May 11, 2020. Turan B, Budhwani H, Fazeli PL, Browning WR, Raper JL, Mugavero MJ, et al. How does stigma affect people living with HIV? The mediating roles of internalized and anticipated HIV stigma in the effects of perceived community stigma on health and psychosocial outcomes. AIDS Behav. 2017; 21: 283–291. https://doi.org/10.1007/s10461-016-1451-5. James PB, Wardle J, Steel A, Adams J. An assessment of Ebola-related stigma and its association with informal healthcare utilisation among Ebola survivors in Sierra Leone: a cross sectional study. BMC Public Health. 2020; 20: 182. https://doi.org/10.1186/s12889-020-8279-7. Aljazeera, 2020. Iran: Over 700 Dead after Drinking Alcohol to Cure Coronavirus. Aljazeera. Available at: https://www.aljazeera.com/ news/2020/04/iran-700-dead-drinking-alcohol-cure-coronavirus200427163529629.html. (Accessed June 4, 2020) Delirrad M, Mohammadi AB, 2020. New methanol poisoning outbreaks in Iran following COVID-19 pandemic. Alcohol Alcohol. 55: 347–348. https://doi.org/10.1093/alcalc/agaa036. Hassanian-Moghaddam H, Zamani N, Kolahi A-A, McDonald R, Hovda KE. Double trouble: methanol outbreak in the wake of the COVID-19 pandemic in Iran-a cross-sectional assessment. Crit Care. 2020; 24: 402. https://doi.org/10.1186/s13054-020-03140-w. Soltaninejad K. Methanol Mass Poisoning Outbreak: A Consequence of COVID-19 Pandemic and Misleading Messages on Social Media. Int J Occup Environ Med. 2020;11(3):148-150. https://dx.doi.org/10.34172%2Fijoem.2020.1983. Islam MS, Sarkar T, Khan SH, Kamal AM, Hasan SMM, Kabir A, et al. COVID-19–Related Infodemic and Its Impact on Public Health: A Global Social Media Analysis. Am J Trop Med Hyg. 2020; 00(0):1–9. https://doi.org/10.4269/ajtmh.20-0812. Hawryluck L, Gold W, Robinson S, Pogorski S, Galea S, Styra R. SARS control and psychological effects of quarantine, Toronto, Canada. Emerg Infect Dis. 2004;10(7):1206–1212. https://dx.doi.org/10.3201%2Feid1007.030703. Lee S, Chan LYY, Chau AAM, Kwok KPS, Kleinman A. The experience of SARS-related stigma at Amoy Gardens. Soc Sci Med. 2005; 61(9): 2038-2046. https://doi.org/10.1016/j.socscimed.2005.04.010. Yoon MK Kim SY Ko HS Lee MS. System effectiveness of detection, brief intervention and refer to treatment for the people with post-traumatic emotional distress by MERS: a case report of community-based proactive intervention in South Korea. Int J Ment Health Syst. 2016; 10: 51. https://doi.org/10.1186/s13033-016-0083-5. Reynolds DL, Garay JR, Deamond SL, Moran MK, Gold W, Styra R. Understanding, compliance and psychological impact of the SARS quarantine experience. Epidemiol Infect. 2008; 136: 997-1007. https://dx.doi.org/10.1017%2FS0950268807009156. Marjanovic Z, Greenglass ER, Coffey S. The relevance of psychosocial variables and working conditions in predicting nurses' coping strategies during the SARS crisis: an online questionnaire survey. Int J Nurs Stud. 2007; 44(6): 991-998. https://doi.org/10.1016/j.ijnurstu.2006.02.012. Bai Y, Lin C-C, Lin C-Y, Chen J-Y, Chue C-M, Chou P. Survey of stress reactions among health care workers involved with the SARS outbreak. Psychiatr Serv. 2004; 55: 1055-1057. https://doi.org/10.1176/appi.ps.55.9.1055. Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/Guidelinesforhomequarantine.pdf [Accessed on 25 August 2020]. Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/RevisedguidelinesforHomeIsolationofverymildpresymptomaticCOVID19cases10May2020.pdf [Accessed on 25 August 2020]. Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/AdvisoryformanagingHealthcareworkersworkinginCOVIDandNonCOVIDareasofthehospital.pdf (Accessed on 25 August 2020). Ministry of Health and Family Welfare. Available at: https://www.mohfw.gov.in/pdf/RevisedguidelinesforInternationalArrivals02082020.pdf [Accessed on 25 August 2020]. Cost of the lockdown? Over 10% of GDP loss for 18 states. Available at: https://timesofindia.indiatimes.com/india/cost-of-the-lockdown-over-10-of-gdp-loss-for-18-states/articleshow/76028826.cms [Accessed on 21 August 2020]. Jorda O, Singh SR, Taylor AM. Longer-Run Economic Consequences of Pandemics. Federal Reserve Bank of San Francisco Working Paper. 2020-09. https://doi.org/10.24148/wp2020-09. Firdaus G. Mental well‑being of migrants in urban center of India: Analyzing the role of social environment. Indian J Psychiatry. 2017; 59:164‑ https://doi.org/10.4103/psychiatry.indianjpsychiatry_272_15. National Crime Record Bureau. Annual Crime in India Report. New Delhi, India: Ministry of Home Affairs; 2018. 198 migrant workers killed in road accidents during lockdown: Report. Available at: https://www.hindustantimes.com/india-news/198-migrant-workers-killed-in-road-accidents-during-lockdown-report/story-hTWzAWMYn0kyycKw1dyKqL.html [Accessed on 25 August 2020]. Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020; 20:689-96. https://doi.org/10.1016/S1473-3099(20)30198-5. Dalton L, Rapa E, Stein A. Protecting the psychological health of through effective communication about COVID-19. Lancet Child Adolesc Health. 2020;4(5):346-347. https://doi.org/10.1016/S2352-4642(20)30097-3. Centre for Disease Control. Helping Children Cope with Emergencies. Available at: https://www.cdc.gov/childrenindisasters/helping-children-cope.html [Accessed on 25 August 2020]. Liu JJ, Bao Y, Huang X, Shi J, Lu L. Mental health considerations for children quarantined because of COVID-19. Lancet Child & Adolesc Health. 2020; 4(5):347-349. https://doi.org/10.1016/S2352-4642(20)30096-1. Sprang G, Silman M. Posttraumatic Stress Disorder in Parents and Youth After Health-Related Disasters. Disaster Med Public Health Prep. 2013;7(1):105-110. https://doi.org/10.1017/dmp.2013.22. Rehman U, Shahnawaz MG, Khan NH, Kharshiing KD, Khursheed M, Gupta K, et al. Depression, Anxiety and Stress Among Indians in Times of Covid-19 Lockdown. Community Ment Health J. 2020:1-7. https://doi.org/10.1007/s10597-020-00664-x. Cao W, Fang Z, Hou, Han M, Xu X, Dong J, et al. The psychological impact of the COVID-19 epidemic on college students in China. Psychiatry Research. 2020; 287:112934. https://doi.org/10.1016/j.psychres.2020.112934. Wang C, Zhao H. The Impact of COVID-19 on Anxiety in Chinese University Students. Front Psychol. 2020; 11:1168. https://dx.doi.org/10.3389%2Ffpsyg.2020.01168. Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, et al. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry 2020;7(3): e14. https://doi.org/10.1016/s2215-0366(20)30047-x. Lai J, Ma S, Wang Y, Cai Z, Hu J, Wei N, et al. Factors associated with mental health outcomes among health care workers exposed to coronavirus disease 2019. JAMA Netw Open 2020;3(3): e203976. https://doi.org/10.1001/jamanetworkopen.2020.3976. Lancee WJ, Maunder RG, Goldbloom DS, Coauthors for the Impact of SARS Study. Prevalence of psychiatric disorders among Toronto hospital workers one to two years after the SARS outbreak. Psychiatr Serv. 2008;59(1):91-95. https://dx.doi.org/10.1176%2Fps.2008.59.1.91. Tam CWC, Pang EPF, Lam LCW, Chiu HFK. Severe acute respiratory syndrome (SARS) in Hongkong in 2003: Stress and psychological impact among frontline healthcare workers. Psychol Med. 2004;34 (7):1197-1204. https://doi.org/10.1017/s0033291704002247. Lee SM, Kang WS, Cho A-R, Kim T, Park JK. Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients. Compr Psychiatry. 2018; 87:123-127. https://dx.doi.org/10.1016%2Fj.comppsych.2018.10.003. Koh D, Meng KL, Chia SE, Ko SM, Qian F, Ng V, et al. Risk perception and impact of severe acute respiratory syndrome (SARS) on work and personal lives of healthcare workers in Singapore: What can we learn? Med Care. 2005;43(7):676-682. https://doi.org/10.1097/01.mlr.0000167181.36730.cc. Verma S, Mythily S, Chan YH, Deslypere JP, Teo EK, Chong SA. Post-SARS psychological morbidity and stigma among general practitioners and traditional Chinese medicine practitioners in Singapore. Ann Acad Med Singap. 2004; 33(6):743e8. Yeung J, Gupta S. Doctors evicted from their homes in India as fear spreads amid coronavirus lockdown. CNN World. 2020. Available at: https://edition.cnn.com/2020/03/25/asia/india-coronavirus-doctors-discrimination-intl-hnk/index.html. [Accessed on 24 August 2020] Violence Against Women and Girls: the Shadow Pandemic. UN Women. 2020. May 3, 2020. Available at: https://www.unwomen.org/en/news/stories/2020/4/statement-ed-phumzile-violence-against-women-during-pandemic. [Accessed on 24 August 2020]. Gearhart S, Patron MP, Hammond TA, Goldberg DW, Klein A, Horney JA. The impact of natural disasters on domestic violence: an analysis of reports of simple assault in Florida (1999–2007). Violence Gend. 2018;5(2):87–92. https://doi.org/10.1089/vio.2017.0077. Sahoo S, Rani S, Parveen S, Pal Singh A, Mehra A, Chakrabarti S, et al. Self-harm and COVID-19 pandemic: An emerging concern – A report of 2 cases from India. Asian J Psychiatr 2020; 51:102104. https://dx.doi.org/10.1016%2Fj.ajp.2020.102104. Ghosh A, Khitiz MT, Pandiyan S, Roub F, Grover S. Multiple suicide attempts in an individual with opioid dependence: Unintended harm of lockdown during the COVID-19 outbreak? Indian J Psychiatry 2020; [In Press]. The Economic Times. 11 Coronavirus suspects flee from a hospital in Maharashtra. March 16 2020. Available at: https://economictimes.indiatimes.com/news/politics-and-nation/11-coronavirus-suspects-flee-from-a-hospital-in-maharashtra/videoshow/74644936.cms?from=mdr. [Accessed on 23 August 2020]. Xiang Y, Yang Y, Li W, Zhang L, Zhang Q, Cheung T, et al. Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. The Lancet Psychiatry 2020;(3):228–229. https://doi.org/10.1016/S2215-0366(20)30046-8. Van Bortel T, Basnayake A, Wurie F, Jambai M, Koroma A, Muana A, et al. Psychosocial effects of an Ebola outbreak at individual, community and international levels. Bull World Health Organ. 2016;94(3):210–214. https://dx.doi.org/10.2471%2FBLT.15.158543. Kumar A, Nayar KR. COVID 19 and its mental health consequences. Journal of Mental Health. 2020; ahead of print:1-2. https://doi.org/10.1080/09638237.2020.1757052. Gupta R, Grover S, Basu A, Krishnan V, Tripathi A, Subramanyam A, et al. Changes in sleep pattern and sleep quality during COVID-19 lockdown. Indian J Psychiatry. 2020; 62(4):370-8. https://doi.org/10.4103/psychiatry.indianjpsychiatry_523_20. Duan L, Zhu G. Psychological interventions for people affected by the COVID-19 epidemic. Lancet Psychiatry. 2020;7(4): P300-302. https://doi.org/10.1016/S2215-0366(20)30073-0. Dubey S, Biswas P, Ghosh R, Chatterjee S, Dubey MJ, Chatterjee S et al. Psychosocial impact of COVID-19. Diabetes Metab Syndr. 2020; 14(5): 779–788. https://dx.doi.org/10.1016%2Fj.dsx.2020.05.035. Wright R. The world's largest coronavirus lockdown is having a dramatic impact on pollution in India. CNN World; 2020. Available at: https://edition.cnn.com/2020/03/31/asia/coronavirus-lockdown-impact-pollution-india-intl-hnk/index.html. [Accessed on 23 August 2020] Foster O. ‘Lockdown made me Realise What’s Important’: Meet the Families Reconnecting Remotely. The Guardian; 2020. Available at: https://www.theguardian.com/keep-connected/2020/apr/23/lockdown-made-me-realise-whats-important-meet-the-families-reconnecting-remotely. (Accessed on 23 August 2020) Bilefsky D, Yeginsu C. Of ‘Covidivorces’ and ‘Coronababies’: Life During a Lockdown. N. Y. Times; 2020. Available at: https://www.nytimes.com/2020/03/27/world/coronavirus-lockdown-relationships.html [Accessed on 23 August 2020]

: Neurological disorders, such as epilepsy, dementia, Parkinson’s disease, and Alzheimer’s disease, occur due to disorganization of the neurons in the nervous system. Disturbances in the nervous system cause problems with memory, senses and moods. In order to treat such disorders, scientists have been working extensively by using different approaches. Nanoneurotechnology has emerged as a promising tool to manage these complicated disorders, where nanoparticles with their tunable properties such as size, shape, increased solubility, biodegradability, surface area and sharp penetration through the biological barriers target the central nervous system. This technology targets damaged neurons without affecting healthy neurons and Blood-Brain Barrier (BBB). In this review, we discuss neurological disorders and challenges in the diagnosis and treatment of neurological disorders by emphasizing the role of tailorable gold nanoparticles for therapeutic drug approaches.

Abstract MicroRNAs (miRNAs) are small non-coding molecules that play a pivotal part in brain development and the processes of establishment and maintenance of dendrites and neurite outgrowth by modulating gene expression. Dysregulation of miRNAs has been linked with neurological disorders. Exogenous miRNAs are unstable in the plasma due to degradation by nucleases; hence, choosing a harmless and effective delivery mode is crucial in the quest for miRNA-based therapeutics to treat neurological disorders. This review aims to shed light on the emerging role of nanotechnology-based approaches using miRNAs to treat neurodegenerative disorders. Nanotechnology encompasses a broad spectrum of applications, one of which is its role in developing nanoscale drug delivery systems. Nanotechnology-based drug delivery systems have attracted the attention of researchers due to the superiority of this mode over conventional treatment systems in terms of their favorable attributes such as bio-compatibility, bio-degradability, extremely small size, and the ability to cross the blood-brain barrier. This review explores nanotechnology-based approaches using miRNAs highlighting the use of viral vectors as well as non-viral vectors (such as exosomes, liposome nanoparticles, gold and magnetic nanoparticles, dendrimer-based nanoparticles, polymeric nanoparticles) to treat neurodegenerative disorders.