Central Nervous Disorders Research Articles

Virtual reality during gait training: does it improve gait function in persons with central nervous system movement disorders? A systematic review and meta-analysis.

During gait training in persons with central nervous system (CNS) movement disorders, virtual reality (VR) can offer added value by providing task-specific gait training in more interactive and motivating environments. To summarize current evidence for the effectiveness of VR-enhanced gait training in persons with CNS movement disorders. PubMed, Web of Science and CENTRAL were systematically searched for studies using VR during walking to improve gait outcomes (spatiotemporal, functional, kinematic and kinetic). Meta-analyses were performed to estimate pooled effects. Eighteen studies with in total 337 patients were included (12 studies with people post-stroke, 4 with multiple sclerosis, 1 with Parkinson's disease, 1 with traumatic brain injury). Spatiotemporal and functional parameters significantly improved in each population after the VR training. Compared to gait training without VR, differences in favor of VR were found for spatiotemporal and functional parameters only in people post-stroke. VR-enhanced gait training is an effective method to improve spatiotemporal and functional parameters in persons with CNS movement disorders. Current evidence supports that, in comparison to training without VR, for people post-stroke VR-enhanced gait training is more effective to improve gait function. Future research regarding other outcome measures and other CNS movement disorders is necessary.

Could the inhibitor of DNA binding 2 and 4 play a role in white matter injury?

White matter injury (WMI) prevents the normal development of myelination, leading to central nervous system myelination disorders and the production of chronic sequelae associated with WMI, such as chronic dyskinesia, cognitive impairment and cerebral palsy. This results in a large emotional and socioeconomic burden. Decreased myelination in preterm infant WMI is associated with the delayed development or destruction of oligodendrocyte (OL) lineage cells, particularly oligodendrocyte precursor cells (OPCs). The development of cells from the OL lineage involves the migration, proliferation and different stages of OL differentiation, finally leading to myelination. A series of complex intrinsic, extrinsic and epigenetic factors regulate the OPC cell cycle withdrawal, OL lineage progression and myelination. We focus on the inhibitor of DNA binding 2 (ID2), because it is widely involved in the different stages of OL differentiation and genesis. ID2 is a key transcription factor for the normal development of OL lineage cells, and the pathogenesis of WMI is closely linked with OL developmental disorders. ID4, another family member of the IDs protein, also plays a similar role in OL differentiation and genesis. ID2 and ID4 belong to the helix-loop-helix family; they lack the DNA-binding sequences and inhibit oligodendrogenesis and OPC differentiation. In this review, we mainly discuss the roles of ID2 in OL development, especially during OPC differentiation, and summarize the ID2-mediated intracellular and extracellular signaling pathways that regulate these processes. We also discuss ID4 in relation to bone morphogenetic protein signaling and oligodendrogenesis. It is likely that these developmental mechanisms are also involved in the myelin repair or remyelination in human neurological diseases.

A Smartphone Application for Automated Decision Support in Cognitive Task Based Evaluation of Central Nervous System Motor Disorders

New technology enables constant boost to the powers of mobile devices, which in the previous years have transformed from simple mobile phones to smart phones. Computational powers of these electronics enable actions that previously were possible only for computers. By the use of special applications, we may benefit from sensors and multimedia capabilities of operating systems. Therefore, a new era for devoted implementations opens, in which a smart application can take a role of computing system to estimate the symptoms of diseases by evaluating signals coming from a human body. We propose a model of an application implemented for mobile android systems, which can be used for examination of central nervous system motor disorders occurring in patients suffering from Huntington (HD), Alzheimer, or Parkinson diseases. In particular, the model tracks tremors (involuntary movements), and cognitive (memory loss or dementia) impairments using touch and visual stimulus modalities. The proposed model interprets the symptoms from human bodies that indicate one of the diseases of the nervous system. Pre-processing of collected data for feature extraction is executed on a mobile device by using core functionality and methods provided in android's application programming interface. The information is evaluated by a back-propagation neural network classifier and the result is presented to the end user. The system is able to contact medical supervision and provide an assistance from the clinic. The system uses a collected dataset of 1928 records, taken from 11 HD patients and 11 healthy persons in Lithuania, to gather statistics about examinations and presents the results as medical evaluation with prediction on the state of health. The accuracy of recognition of early, prodromal symptoms for central nervous system motor disorders is 86.4% (F-measure 0.859). The app (available on Google Play) is easy to use and is efficient tool for decision support in medical examinations. The use of intelligent apps which can help to evaluate neurodegenerative disorders is an important enhancement to medical diagnosis. The developed smartphone app supports the doctor with additional results that are easy to compare with other examinations. This kind of examination is a nice change from classic stereotypes, especially for younger age patients, who are used to various aspects of information technology.

Magnetic resonance imaging findings in idiopathic sudden sensorineural hearing loss.

Background The unpredictability in presenting signs and symptoms of idiopathic sudden sensorineural hearing loss (SSNHL) presents a notable diagnostic challenge for clinicians. Previous studies have confirmed the potentially important role of magnetic resonance imaging (MRI) in the diagnosis and prognostication of idiopathic SSNHL to guide definitive medical therapy, but correlations of these findings with outcomes remain controversial. Purpose To evaluate and identify magnetic resonance imaging (MRI) findings associated with idiopathic sudden sensorineural hearing loss (SSNHL). Material and Methods Sixty-eight patients with a documented diagnosis of idiopathic SSNHL and 20 controls underwent 1.5-T or 3-T MRI of the brain. Age, gender, ethnicity, associated co-morbidities, and audiometry findings were also recorded. Statistical analysis was performed to compare outcome measures between idiopathic SSNHL and control groups. Results The mean age of the cohort was 57 ± 17 years, with a male-to-female ratio of 1:1.1. MRI findings include 25.0% ( P = 1.000) with chronic microangiopathic disease, 14.7% ( P = 0.165) with temporal bone aberrations, 13.2% ( P = 0.165) with facial and/or vestibulocochlear nerve complex changes, 11.8% ( P = 1.000) with venous malformations, 8.8% ( P = 0.104) with arterial malformations, and 8.8% ( P = 0.184) with cerebral and/or brainstem parenchymal disease. Conclusion Arteriovenous malformations and central neurologic disease are not directly associated with idiopathic SSNHL on MRI. However, visualized signal changes of inner ear structures and facial/vestibulocochlear nerve complex support previously postulated theories, which include viral as well as inflammatory processes in the development of idiopathic SSNHL.

Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors.

The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-D-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of L-arginine, can regulate ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders. In this review, we will focus on the pathophysiological aspects of the neurological disorders regulated by these ion channels and receptors, and their interaction with agmatine in CNS injury.

Drug utilization pattern in adult medical intensive care unit of a tertiary care hospital

Aims: This study aims to evaluate the drug utilization pattern in terms of Defined Daily Dose (DDD) in adult Medical Intensive Care Unit. Methods: In this prospective study conducted over a period of 8 months, data pertaining to all adult (age ≥18 years) patients' demography, diagnosis, treatment, and laboratory investigation were collected. The drugs were categorized by anatomical therapeutic classification, and their DDD was calculated. Results: A total of 452 patients were evaluated, of which 62.6% were males. The most common reason for hospitalization was cardiovascular disorder (21.4%), followed by respiratory disorder (21%) and central nervous disorder (20%). An average of 9.9 drugs was prescribed per patient. Nearly 52% of drugs were administered parenteral, 43% were oral and 5% were either nebulization or topical. Among the drugs prescribed, the most common drugs were pantoprazole, ondansetron, aspirin, furosemide, and atorvastatin and most common antimicrobials were ceftriaxone followed by piperacillin + tazobactam and metronidazole. Conclusions: Drug utilization produces an important impact on quantitative data for Intensive Care Unit patients and should be conducted regularly so as to understand the drug consumption as well as for protocol implementation to improve the quality of health care.

Selective and Sensitive Mass Spectrometric Identification of Immune Complex Antigens in Cerebrospinal Fluid.

Comprehensive identification of immune complex antigens (IC-antigens) in cerebrospinal fluid (CSF) is useful to provide insights into pathophysiology and could form the basis for novel diagnostic and treatment strategies for central nervous system autoimmune diseases and other neurological disorders. Immune complexome analysis is the method for comprehensively identifying IC-antigens in biological fluids (such as serum and CSF). Here, we describe IC-antigens detection method; specifically, ICs in CSF are captured and are subjected to papain-digestion elution and tryptic digestion, and are analyzed by nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS).

Nervous system involvement in Behçet's syndrome.

Neurological involvement in Behçet's syndrome is defined as 'the occurrence of neurological symptoms and signs in a patient who meets the International Diagnostic Criteria for BS not otherwise explained by any other known systemic or neurological disease or treatment, and in whom objective abnormalities consistent with neuro-Behçet's syndrome (NBS) are detected either on neurological examination, neuroimaging studies (magnetic resonance imaging [MRI]), and/or on cerebrospinal fluid (CSF) examination'. Given that the neurological involvement of Behçet's syndrome carries a poor prognosis, we aimed to describe the differential diagnosis of NBS and highlight the different radiological patterns together with the treatment options. Two distinct MRI patterns of spinal cord involvement in Behçet's syndrome according to T2-weighted axial images were described: 'Bagel Sign' pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and 'Motor Neuron' pattern: a symmetric involvement of the anterior horn cells. Infliximab prevents patients from having further attacks and even led to improvement in the neurological examination. As the treatment options completely differ, a NBS diagnosis should be carefully made in patients with clinical and MRI features mimicking other central nervous system inflammatory disorders.

Neurological Involvement in Systemic Lupus Erythematosus (SLE): Our Recent Experience

Introduction: The central, psychiatric and peripheral neurological manifestations of lupus are among the most severe visceral disorders and are grouped under the general term of “neuro-psychiatric systemic lupus erythematosus” (NPSLE). We conducted a cross-sectional observational study within our Department of Internal Medicine aimed at describing the clinical and evolutionary aspects of central neurological disorders of SLE, excluding lupus myelopathy. Patients and Methods: This was a retrospective and observational cross-sectional study carried out from 1 January 2015 to 31 October 2017, in the Department of Internal Medicine of Aristide le Dantec University Hospital in Dakar (Senegal). All patients hospitalized during this period who met the 1997 ACR classification criteria of SLE and who presented with a central neuropsychiatric syndrome attributable to SLE (as defined by ACR 1999) were included. Patients with isolated headache, acute myelitis or secondary neurological involvement attributable to a toxic, metabolic, infectious or tumour-related cause were excluded from our study. Results: During the study period, 10 patients with neuropsychiatric lupus involvement were treated at our institution, including 9 women and 1 man; the median age was 29 years (20 - 55 years). Neurological involvement occurred during the course of lupus evolution in 9/10 cases. The median time to SLE evolution was 18 months (0 - 60 months). Neuropsychiatric syndromes as defined by the 1999 ACR were commonly associated and more than half of our patients had multiple neuropsychiatric syndromes. There were 5 cases of confusion syndrome and coma, 4 cases of seizure, 3 cases of psychosis, 2 cases of acute cerebrovascular disease and 1 case of aseptic meningitis. Among the extra-neurological manifestations of SLE, haematological and dermatological involvements were common. Renal involvement affected half of the patients. The other manifestations were: polyarthritis in 3 patients, serositis in 2 patients, 5 cases of fever, 4 cases of deterioration of the general state, and one isolated case of ophthalmological involvement. Therapeutically, 8 patients received a bolus of methylprednisolone and 3 patients received a bolus of cyclophosphamide. Oral corticosteroids and hydroxychloroquine were administered to all patients, and azathioprine was administered in 2 patients. The evolution was favorable in 4 patients, other 2 patients maintained neurological sequelae and 2 patients were transferred to intensive care. Death was recorded in 4 patients. Conclusion: Neuropsychiatric manifestations of lupus are rare and sometimes severe, potentially life-threatening. In our patients, we have identified some of the most severe neurological syndromes according to the ACR nomenclature. The neurological involvement is exceptionally revealing, as these syndromes are often associated and integrated into a systemic context of lupus. The evolution is rapidly unfavorable and requires early diagnosis and optimal management.

2039. New York State 2016–2018: Progression from Candida auris Colonization to Bloodstream Infection

BackgroundNew York State (NYS) is experiencing a continuing outbreak of Candida auris, first identified in 2016. Patients who are colonized asymptomatically with C. auris can progress to bloodstream infection (BSI).MethodsColonized patients with positive nares or axilla/groin C. auris cultures were followed prospectively. Laboratories, hospitals and skilled nursing facilities reported C. auris clinical infections to the NYS Department of Health. Patient demographics, clinical history, hospital admission, procedures, and outcomes data were obtained using a standardized case report form. Patient-days were determined from date of first positive colonization to date of first positive clinical isolate, death, or March 30, 2018, whichever was first.ResultsBetween September 28, 2016 and March 30, 2018, 187 C. auris colonized patients were identified. Of these, seven progressed to BSI during at least 24,781 patient days of follow-up (median: 98 patient-days, range 0–548 days.) The median time from date of first colonization to date of BSI was 86 days (range 3–310 days). The median patient age at time of colonization was 71 years (range 57–89 years). Between colonization and BSI, patients had a median of five admissions in healthcare facilities (range 1–12). All patients had central neurologic disease, gastrostomy tubes, chronic wounds, and vascular lines at time of BSI. All patients had a positive culture for one or more other multi-drug resistant organism within 90 days of a positive C. auris culture, and all received antibiotics in the 30 days before BSI. Six (86%) patients received mechanical ventilation and had tracheostomies. Five (71%) patients had diabetes. Four (57%) had vascular lines replaced in the 30 days before BSI onset. Two (29%) cases had gastrostomy tube replacement between colonization and BSI. One patient died a week after C. auris BSI; a second died 4 months later.ConclusionIn NYS, 4% of C. auris colonized patients developed BSI, a rate of 0.3 BSI per 1,000 patient-days. BSI patients have portals of entry such as indwelling medical devices and wounds. Neurologic disease and diabetes may be risk factors for BSI. Meticulous aseptic technique for invasive procedures, device and wound care may help prevent C. auris BSI in colonized patients.Disclosures All authors: No reported disclosures.

Alpha-lipoic acid in the treatment of psychiatric and neurological disorders: a systematic review.

Despite the existence of many preclinical studies, scientific evidence is lacking on the clinical use of alpha-lipoic acid (ALA) for central nervous system disorders. Therefore, we aimed at revising the literature concerning the use of ALA for the treatment of psychiatric and neurological conditions and to point out what is missing for the introduction of this antioxidant to this purpose. For this systematic review we performed a search using PubMed and SCOPUS databases with the following keywords: "alpha-Lipoic Acid AND central nervous system OR psychiatric disorders OR neurological disorders OR mood disorders OR anxiety OR psychosis OR Alzheimer OR Parkinson OR stroke". The total number of references found after automatically and manually excluding duplicates was 1061. After primary and secondary screening 32 articles were selected. Regarding psychiatric disorders, the studies of ALA in schizophrenia are advanced being ALA administration related to the improvement of schizophrenia symptoms and side effects of antipsychotic medication. In neurological disorders, ALA as a supplement was effective in the prevention of Alzheimer disease progression. For stroke, the use of the supplement ALAnerv® (containing 300mg ALA) presented important results, since it was observed a reversal of clinical parameters and oxidative imbalance in these patients. For other neurological conditions, such as encephalopathy, multiple sclerosis, traumatic brain injury, mitochondrial disorders and migraine, the results are still preliminary. Overall, there is a need of well-designed clinical trials to enhance the clinical evidences of ALA effects for the treatment of neurological and psychiatric conditions.

Characteristics and management of congenital anophthalmos and microphthalmos at a tertiary eye hospital

ABSTRACTPurpose: The purpose of the study is to evaluate demographic data and outcomes of the management of congenital anophthalmia/microphthalmia.Methods: This retrospective, descriptive, cross-sectional study evaluated patients with congenital anophthalmia/microphthalmia managed from 2004 to 2014 at a tertiary hospital in Saudi Arabia. Data were collected on patient age, gender, cause, orbital status, laterality, systemic comorbidities, ocular evaluation, and management (type of surgery, type of orbital implant, and complications). The main outcome measure was the ability to hold the prosthesis.Results: The study sample was composed of 513 eyes/sockets of 365 patients. Two-hundred and seventeen (59.4%) patients were unilateral cases. Forty-one (8%) sockets were due to congenital anophthalmia and 471 (92%) were due to microphthalmia. There were 73.2% isolated cases and 28.5% with systemic involvement. Systemic involvement was more common in bilateral cases. The most commonly associated conditions were central nervous disorders. One-hundred and nineteen (46.7%) cases had parental consanguinity. Two hundred and eighteen eyes/sockets (163 patients) underwent surgery including conjunctival flap (38; 17.4%), evisceration (38; 17.4%), enucleation (16; 7.3%), or procedures to improve the anophthalmic socket volume (45; 20.6%). Volume enhancing procedures included polymethylmethacrylate orbital implants (26; 57.8%), expanders (11; 24.4%), integrated hydroxyapatite or polyethylene implants (2; 4.4%), and dermis-fat graft (6; 13.3%). In most cases, clinical or surgical management resulted in a successful outcome.Conclusion: Anophthalmia/Microphthalmia was detected in 36.5 patients/year. The majority had isolated microphthalmia. Good outcomes were achieved with clinical or surgical management in the majority of cases.

Geriatric Dysphonia: Etiological Analysis in a Rural Hospital in India.

To establish the prevalence of etiological factors for dysphonia in elderly individuals in rural India. Hundred adults aged ≥ 65years, who presented with dysphonia for ≥ 4weeks and underwent detailed clinical evaluation including videolaryngoscopic assessment and other appropriate investigations/evaluation, were included in a retrospective cohort clinical study. Patients were classified into eight groups for further descriptive statistical analysis based on standard diagnostic criteria/guidelines i.e. benign vocal cord lesions, inflammatory disorders of the larynx, laryngeal and hypopharyngeal neoplasms, isolated vocal cord palsy/paresis, presbylaryngis, central neurological disorders affecting laryngeal function, impaired pulmonary function and non specific dysphonia. Mean age was 70.73 ± 4.29years. 58% were aged between 65 and 69years. Overall, the common causes for dysphonia were laryngopharyngeal reflux disease (23%), carcinoma larynx (12%) and presbylaryngis (8%). Inflammatory disorders of the larynx, benign vocal cord lesions and laryngeal/hypopharyngeal malignancies were the commonest causes for dysphonia in individuals aged between 65 and 74years. Presbylaryngis and systemic causes were the commonest among individuals aged 75-89years. 63 males and 37 females met the inclusion criteria. The most common cause for dysphonia among females was laryngopharyngeal reflux disease (17%), followed by vocal palsy (5%) and spasmodic dysphonia (4%). Carcinoma larynx (12%) was the most common cause for dysphonia among males, followed by laryngopharyngeal reflux (6%) and presbylaryngis (6%). Geriatric dysphonia is an often overlooked symptom of greater underlying disease as evidenced in this study. With its impact on the quality of life in this age group and life expectancy in the rural population, dysphonia requires early detection, prompt evaluation and appropriate management.

Feasibility and Utility of Tele-Neurorehabilitation Service in India: Experience from a Quaternary Center.

Background:Neurological rehabilitation service in developing countries like India is a great challenge in view of limited resources and manpower. Currently, neurological rehabilitation with a multidisciplinary team is limited to a few major cities in the country. Tele-neurorehabilitation (TNR) is considered as an alternative and innovative approach in health care. It connects the needy patients with the health-care providers with minimum inconvenience and yields cost-effective health care.Aim:The aim of this study was to study the socioclinical parameters, feasibility, and utility of TNR services in India.Methodology:A retrospective file review of TNR consultations provided through Telemedicine Center at a quaternary hospital-based research center in south India between August 2012 and January 2016.Results:A total of 37 consultations were provided to the patients belonging to four districts of Karnataka. The mean age of the patients was 34.7 (±19.5) years, 23 (62.1%) were aged between 19 and 60 years, and 31 (83.8%) were male. Thirty-one patients (83.8%) had central nervous system-related disorders such as stroke, cerebral palsy, and tubercular meningitis with sequelae or neuromuscular disorders such as Guillain–Barre Syndrome and Duchenne muscular dystrophy. Twelve patients (32.4%) were advised to consult higher centers in the vicinity, and the rest was referred to the district hospital.Conclusion:The findings suggest that TNR services are feasible, effective, and less resource intensive in delivering quality telemedicine care in India. More clinical studies are required to elucidate its full utility at different levels and in different parts of the country.

Intercellular Communication Is Key for Protective IFNα/β Signaling During Viral Central Nervous System Infection.

A variety of viruses can induce central nervous system (CNS) infections and neurological diseases, although the incidence is rare. Similar to peripheral infections, IFNα/β induction and signaling constitutes a first line of defense to limit virus dissemination. However, CNS-resident cells differ widely in their repertoire and magnitude of both basal and inducible components in the IFNα/β pathway. While microglia as resident myeloid cells have been implicated as prominent sentinels of CNS invading pathogens or insults, astrocytes are emerging as key responders to many neurotropic RNA virus infections. Focusing on RNA viruses, this review discusses the role of astrocytes as IFNα/β inducers and responders and touches on the role of IFNα/β receptor signaling in regulating myeloid cell activation and IFNγ responsiveness. A summary picture emerges implicating IFNα/β not only as key in establishing the classical "antiviral" state, but also orchestrating cell mobility and IFNγ-mediated effector functions.

Acute Management of Optic Neuritis: An Evolving Paradigm.

The current management of acute optic neuritis (ON) is focused on expediting visual recovery through the use of high-dose intravenous corticosteroids. The recent identification of specific autoantibodies associated with central nervous system inflammatory disorders has provided novel insights into immune targets and mechanisms that impact the prognosis, treatment, and recurrence of ON. Therefore, neurologists and ophthalmologists need to be aware of clinical, laboratory, and imaging findings that may provide important clues to the etiology of ON and the potential need for aggressive management. Moving forward, rapid and accurate diagnosis of inflammatory ON will likely be critical for implementing clinical care that optimizes short-term and long-term therapeutic outcomes.

Vértigo fóbico, una patología silente

El vértigo fóbico se constituye como una patología dentro de las alteracionessomatomorfas que cursan con trastornos del balance, relacionadas a un procesode desajuste sensorial aferente, con repercusiones eferentes especiales que noson evidentes al observador, identificadas, por ejemplo, por un aumento en lospatrones de propiocepción detectados por electroposturografía. Las características clínicas de estos pacientes están descritas como eventos vertiginosos no asociados a claros desencadenantes, sino más bien una respuesta muy personal a ambientes particulares normales para otras personas, quienes adicionalmente ofrecen personalidades obsesivas-compulsivas, perfeccionistas autodemandantes, incluso depresivas dentro de un contexto que culmina en inestabilidad. No se identifican alteraciones auditivas concomitantes, ni tampoco neurológicas centrales, por lo que su diagnóstico diferencial podría hacerse evidente denotando los diagnósticos más relevantes, tanto psicogénicos como orgánicos, aportados por Brandt y colaboradores.

SNAP-25 Puts SNAREs at Center Stage in Metabolic Disease

Synaptosomal Associated Protein of 25 kD (SNAP-25) is an essential protein contributing 2 out of 4 α-helices in the formation of the core soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex which mediates regulated membrane fusion. Regulated exocytosis is a strictly controlled event in eukaryotic cells mediating important homeostatic processes and cellular communications. Altered release of neurotransmitters or hormones is usually considered as part of the progressing pathophysiology of central neurological or peripheral metabolic disorders. However, the molecular changes which precede and initiate disturbed secretion of neurotransmitters and hormones are still unclear. We have explored an alternative hypothesis; that a minor modification in the machinery mediating regulated exocytosis, instead, may underlie the origin of the diseases associated with altered secretion of neurotransmitters and hormones. Possibly, certain modifications to genes encoding for SNAREs or proteins affecting SNARE function may increase the susceptibility to develop disease and its progression can be accelerated when combined with aging and life style factors. To test this theory, we genetically manipulated the Snap25 gene to express only one of the two alternatively spliced isoforms, SNAP-25a. SNAP-25b-deficient mice demonstrated alterations in synaptic transmission and increased insulin secretion which, with time, spontaneously progressed into a pronounced metabolic disease, including defects in glucose homeostasis, obesity, liver steatosis and perturbations in central homeostatic signaling. Thus, deregulated function of SNAP-25 and possibly other SNAREs or SNARE-interacting proteins, can, by itself, act as risk factors for the development of metabolic disease. Here, we provide an overview of the peripheral and central consequences of the deregulations in core SNARE complex with focus on SNAP-25.

In Vivo Imaging of Microglia With Multiphoton Microscopy.

Neuroimaging has become an unparalleled tool to understand the central nervous system (CNS) anatomy, physiology and neurological diseases. While an altered immune function and microglia hyperactivation are common neuropathological features for many CNS disorders and neurodegenerative diseases, direct assessment of the role of microglial cells remains a challenging task. Non-invasive neuroimaging techniques, including magnetic resonance imaging (MRI), positron emission tomography (PET) and single positron emission computed tomography (SPECT) are widely used for human clinical applications, and a variety of ligands are available to detect neuroinflammation. In animal models, intravital imaging has been largely used, and minimally invasive multiphoton microcopy (MPM) provides high resolution detection of single microglia cells, longitudinally, in living brain. In this study, we review in vivo real-time MPM approaches to assess microglia in preclinical studies, including individual cell responses in surveillance, support, protection and restoration of brain tissue integrity, synapse formation, homeostasis, as well as in different pathological situations. We focus on in vivo studies that assess the role of microglia in mouse models of Alzheimer’s disease (AD), analyzing microglial motility and recruitment, as well as the role of microglia in anti-amyloid-β treatment, as a key therapeutic approach to treat AD. Altogether, MPM provides a high contrast and high spatial resolution approach to follow microglia chronically in vivo in complex models, supporting MPM as a powerful tool for deep intravital tissue imaging.

Developing an Arabic Screening Test for Adult-Onset Chronic Aphasia

Aim: To develop a time-efficient Arabic test battery for adult-onset chronic aphasia that provides information about the type and the severity of the disorder. Patient and Methods: A total of 90 participants were recruited and divided into 3 groups. The groups consisted of 30 adult-onset post-stroke chronic aphasic patients, 30 adult non-aphasic adults with central neurological disorders, and a group of 30 non-brain-damaged healthy adults. All participants were assessed using the Mansoura Arabic Screening Aphasia Test (MASAT), which consists of 4 main sections: (1) language expression abilities including repetition and naming items, (2) language comprehension questions, (3) fluency, and (4) reading, writing and calculation items. The content validity, internal consistency, clinical validity, and convergent validity of the MASAT were evaluated. Results: The MASAT demonstrated statistically high reliability and validity. The high α-values in all subtotal scores among the 3 groups were judged to denote excellent intercorrelation among the screening test items. Conclusion: The MASAT is a valid and a reliable brief assessment tool that can be completed on the first clinic appointment that detects the type and severity of Arabic-speaking aphasic patients.