36,267 results match your criteria Primary Lateral Sclerosis


Longitudinal Timed Up and Go Assessment in Amyotrophic Lateral Sclerosis: A Pilot Study.

Eur Neurol 2021 Jun 24:1-5. Epub 2021 Jun 24.

Division of Cognitive and Motor Aging, Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA.

Progressive loss of walking ability in amyotrophic lateral sclerosis (ALS) has been scarcely studied as a potential predictive factor for survival in motor neuron disease. We aimed to assess the progression of gait decline and its association with mortality in ALS using the Timed Up and Go test (TUG). Patients were followed up prospectively at the Centre for ALS and Related Disorders in Geneva University Hospitals between 2012 and 2016. Read More

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Respiratory dysfunction in a mouse model of spinocerebellar ataxia type 7.

Dis Model Mech 2021 Jun 23. Epub 2021 Jun 23.

Department of Pediatrics, School of Medicine, Duke University, Durham, NC 27708, USA.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the ataxin-7 gene. Infantile-onset SCA7 patients display extremely large repeat expansions (>200 CAGs) and exhibit progressive ataxia, dysarthria, dysphagia and retinal degeneration. Severe hypotonia, aspiration pneumonia and respiratory failure often contribute to death in affected infants. Read More

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R13 preserves motor performance in SOD1 mice by improving mitochondrial function.

Theranostics 2021 24;11(15):7294-7307. Epub 2021 May 24.

Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Medical Key Subject of Modern Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by death of motor neurons in the brain and spinal cord. However, so far, there is no effective treatment for ALS. In this study, R13, a prodrug of 7,8-dihydroxyflavone, selectively activating tyrosine kinase receptor B (TrkB) signaling pathway, was administered prophylactically to 40-day old SOD1 mice for 90 days. Read More

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Integrated Home-Based Palliative Care in Motor Neuron Disease: A Case Report from Low- Middle Income Country.

J Soc Work End Life Palliat Care 2021 Jun 21:1-5. Epub 2021 Jun 21.

Department of Psychiatric Social Work, NIMHANS, Bengaluru, India.

In many international care guidelines, multidisciplinary palliative care forms a key to optimum management in Motor Neuron Disease (MND). We describe the home-based palliative care interventions for a client with MND and his family from a Low and Middle-income country context. This report also discusses the advantages and challenges of the same with suggestions for sustaining the quality of care for neuro palliative conditions. Read More

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Association Between Globular Glial Tauopathies and Frontotemporal Dementia-Expanding the Spectrum of Gliocentric Disorders: A Review.

JAMA Neurol 2021 Jun 21. Epub 2021 Jun 21.

Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.

Importance: Globular glial tauopathies (GGTs), as defined by a consensus study in 2013, belong to the group of frontotemporal lobar degenerations and expand the spectrum of glial-predominant neurodegenerative diseases. Three neuropathological subtypes of GGT (types I-III) are characterized by phosphorylated tau-immunopositive inclusions that are predominantly in oligodendroglia and/or astroglia in the frontal, temporal, and/or precentral cortices. Type II is largely restricted to the corticospinal system. Read More

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Pentraxin 3 secreted by human adipose-derived stem cells promotes dopaminergic neuron repair in Parkinson's disease via the inhibition of apoptosis.

FASEB J 2021 Jul;35(7):e21748

Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Although adipose-derived human mesenchymal stem cell (hADSC) transplantation has recently emerged as a promising therapeutic modality for Parkinson's disease (PD), its underlying mechanism of action has not been fully elucidated. This study evaluated the therapeutic effects of stereotaxic injection of hADSCs in the striatum of the 6-OHDA-induced mouse model. Furthermore, an in vitro PD model was constructed using tissue-organized brain slices. Read More

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Onasemnogene abeparvovec-xioi: a gene replacement strategy for the treatment of infants diagnosed with spinal muscular atrophy.

Drugs Today (Barc) 2021 Jun;57(6):387-399

Biomedical Sciences Graduate School, The Ohio State University, Columbus, Ohio, USA.

In May of 2019, the adeno-associated virus (AAV)-based gene therapy onasemnogene abeparvovec-xioi (Zolgensma) became the second Food and Drug Administration (FDA)-approved gene therapy with designated use for infants diagnosed with spinal muscular atrophy (SMA). The decision came nearly 10 years after results of the first preclinical models were initially reported. While the journey was an arduous one, the approval was an indication of the remarkable success of the first in-human clinical trials. Read More

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Understanding the role of histone deacetylase and their inhibitors in neurodegenerative disorders: Current targets and future perspective.

Curr Neuropharmacol 2021 Jun 9. Epub 2021 Jun 9.

Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.

Neurodegenerative diseases are the group of pathological conditions that cause motor inc-ordination (jerking movements), cognitive and memory impairments result due to degeneration of neurons in a specific area of the brain. Oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation, neurochemical imbalance and histone deacetylase enzymes (HDAC) are known to play a crucial role in neurodegeneration. HDAC is classified into four categories (class I, II, III and class IV) depending upon their location and functions. Read More

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Human endogenous retrovirus K (HERV-K) env in neuronal extracellular vesicles: a new biomarker of motor neuron disease.

Amyotroph Lateral Scler Frontotemporal Degener 2021 Jun 20:1-8. Epub 2021 Jun 20.

Department of Neurology, Peking University Third Hospital, Beijing, China.

Human endogenous retroviruses (HERVs) have been gradually confirmed to be involved in the onset and progression of motor neuron disease(MND). However, noninvasive detection of HERVs in the central nervous system is lacking. The aim of this study is to verify the relationship between the level of HERV-K env in neuronal extracellular vesicles in plasma and the onset and severity of MND. Read More

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Case Report: Cognitive Conversion in a Non-brazilian VAPB Mutation Carrier (ALS8).

Front Neurol 2021 2;12:668772. Epub 2021 Jun 2.

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.

Amyotrophic lateral sclerosis 8 (ALS8) is a predominantly lower motor neuron syndrome originally described in a Portuguese-Brazilian family, which originated from a common founder. ALS8 is caused by a VAPB mutation and extremely rare in Central Europe. We present a 51-year-old German man with ALS8 who had the P56S VAPB mutation independently of the founder effect. Read More

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Palliative Care Intervention Trials for Adults Living with Progressive Central Nervous System Diseases and Their Caregivers: A Systematic Review.

J Pain Symptom Manage 2021 Jun 17. Epub 2021 Jun 17.

Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, 9030 Old Georgetown Rd, Bethesda, Maryland, 20892, USA; Office of Research Services, Division of Library Services, National Institutes of Health, Bethesda, Maryland, USA.

Context: Interest in implementing palliative care for adults living with progressive central nervous system diseases (PCNSD) and their caregivers is increasing.

Objectives: To inform evidence-based practice and future research by critically evaluating randomized clinical trials (RCTs) investigating palliative care interventions (PCIs) for adults living with PCNSD and their caregivers using self-reported outcomes and the patient- and caregiver-reported outcome measures employed.

Methods: A systematic search using PRISMA methods of EMBASE, PubMed, Scopus, Web of Science databases using index and keyword methods for articles published from inception through 28 February 2021 was performed. Read More

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Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.

Brain 2021 Jun 18. Epub 2021 Jun 18.

The Rockefeller University, New York, NY, 10065 USA.

Dysregulation of glutamatergic neural circuits has been implicated in a cycle of toxicity, believed among the neurobiological underpinning of Alzheimer's disease. Previously, we reported preclinical evidence that the glutamate modulator riluzole, which is FDA-approved for the treatment of amyotrophic lateral sclerosis, has potential benefits on cognition, structural and molecular markers of aging and Alzheimer's disease. The objective of this study was to evaluate in a pilot clinical trial, using neuroimaging biomarkers, the potential efficacy and safety of riluzole in patients with Alzheimer's disease as compared to placebo. Read More

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Overexpression of ferroptosis defense enzyme Gpx4 retards motor neuron disease of SOD1G93A mice.

Sci Rep 2021 Jun 18;11(1):12890. Epub 2021 Jun 18.

Department of Cell Systems & Anatomy, University of Texas Health San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, 78229, USA.

Degeneration and death of motor neurons in Amyotrophic Lateral Sclerosis (ALS) are associated with increased lipid peroxidation. Lipid peroxidation is the driver of ferroptosis, an iron-dependent oxidative mode of cell death. However, the importance of ferroptosis in motor neuron degeneration of ALS remains unclear. Read More

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The economic burden of amyotrophic lateral sclerosis: a systematic review.

Eur J Health Econ 2021 Jun 18. Epub 2021 Jun 18.

Institute for Applied Health Services Research (inav GmbH), Berlin, Germany.

Objectives: This systematic review aimed to comprehensively collect and summarise the current body of knowledge regarding the cost-of-illness of amyotrophic lateral sclerosis, to identify cost-driving factors of the disease and to consider the development of costs over the course of disease. Further, the review sought to assess the methodological quality of the selected studies.

Methods: A systematic review was performed using the databases MEDLINE, Embase, Cochrane Library and PsycINFO. Read More

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Bladder management, severity of injury and period of latency: a descriptive study on 135 patients with spinal cord injury and bladder cancer.

Spinal Cord 2021 Jun 17. Epub 2021 Jun 17.

Clinical Occupational Medicine, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.

Study Design: Longitudinal study.

Objectives: To describe the severity of spinal cord injury/disease (SCI/D), type and management of neurogenic lower urinary tract dysfunction, tumor characteristics, and bladder cancer latency period in SCI/D patients.

Setting: Spinal cord injury centers in Germany, Austria, and Switzerland. Read More

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Pathogenic effect of Gene Variants in People With Amyotrophic Lateral Sclerosis.

Neurology 2021 Jun 16. Epub 2021 Jun 16.

Department of Human Genetics, University of Utah School of Medicine, SLC, UT.

Objective: To identify novel disease associated loci for amyotrophic lateral sclerosis (ALS), we utilized sequencing data and performed and experiments to demonstrate pathogenicity of mutations identified in .

Methods: We analyzed exome sequences of 87 sporadic ALS patients and 324 controls, with confirmatory sequencing in independent ALS cohorts of >2,800 patients. For the top hit, , a regulator of apoptosis, differentiation, and a binding partner as well as homolog of the tumor suppressor gene we assayed mutation effects using and experiments. Read More

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A retrospective analysis of emerging rabies: a neglected tropical disease in Sarawak, Malaysia.

J R Coll Physicians Edinb 2021 06;51(2):133-139

Neurology Department, Hospital Kuala Lumpur, Ministry of Health Malaysia, Kuala Lumpur, Malaysia.

Background: Rabies, a neglected tropical disease (NTD), is a viral infection which is often fatal. Since 2017, a rabies epidemic has been declared in Sarawak, Malaysia. However, there is a lack of local epidemiological data and descriptions of local presentations of this disease. Read More

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HoxD transcription factors define monosynaptic sensory-motor specificity in the developing spinal cord.

Development 2021 Jun 15;148(12). Epub 2021 Jun 15.

Neural Connectivity Development in Physiology and Disease Laboratory, Burke Neurological Institute, White Plains, NY 10605, USA.

The specificity of monosynaptic connections between proprioceptive sensory neurons and their recipient spinal motor neurons depends on multiple factors, including motor neuron positioning and dendrite morphology, axon projection patterns of proprioceptive sensory neurons in the spinal cord, and the ligand-receptor molecules involved in cell-to-cell recognition. However, with few exceptions, the transcription factors engaged in this process are poorly characterized. Here, we show that members of the HoxD family of transcription factors play a crucial role in the specificity of monosynaptic sensory-motor connections. Read More

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[Epiconus Syndrome and Conus Syndrome].

Brain Nerve 2021 Jun;73(6):659-670

Department of Neurology, Chubu Rosai Hospital.

The most caudal part of the spinal cord shows special anatomical characteristics and it contains epiconus (L4-S2 segments), the conus medullaris (S3-S5 segments), and surrounding nerve roots. Lesions of the thoracolumbar junction cause epiconus or conus syndrome. Epiconus syndrome is characterized by segmental muscular weakness and atrophy of one or both lower extremities, often accompanied by foot drop. Read More

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Climate change and neurodegenerative diseases.

Environ Res 2021 Jun 12;201:111511. Epub 2021 Jun 12.

Scuola Superiore Sant'Anna and Centre for Climate Change Studies and Sustainable Actions (3CSA), Pisa, Italy.

The climate change induced global warming, and in particular the increased frequency and intensity of heat waves, have been linked to health problems. Among them, scientific works have been reporting an increased incidence of neurological diseases, encompassing also neurodegenerative ones, such as Dementia of Alzheimer's type, Parkinson's Disease, and Motor Neuron Diseases. Although the increase in prevalence of neurodegenerative diseases is well documented by literature reports, the link between global warming and the enhanced prevalence of such diseases remains elusive. Read More

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Synaptic disruption and CREB-regulated transcription are restored by K channel blockers in ALS.

EMBO Mol Med 2021 Jun 14:e13131. Epub 2021 Jun 14.

Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, Germany.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which is still missing effective therapeutic strategies. Although manipulation of neuronal excitability has been tested in murine and human ALS models, it is still under debate whether neuronal activity might represent a valid target for efficient therapies. In this study, we exploited a combination of transcriptomics, proteomics, optogenetics and pharmacological approaches to investigate the activity-related pathological features of iPSC-derived C9orf72-mutant motoneurons (MN). Read More

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Moxibustion Protects Dopaminergic Neurons in Parkinson's Disease through Antiferroptosis.

Evid Based Complement Alternat Med 2021 16;2021:6668249. Epub 2021 Apr 16.

Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong 518104, China.

Ferroptosis is associated with neural degeneration of dopaminergic neurons in Parkinson's disease (PD). However, how to control the level of ferroptosis in PD remains unclear. Clinically, moxibustion has been used to treat PD and has an apparent therapeutic effect on improving the motor symptoms of PD. Read More

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Dissection, in vivo imaging and analysis of the mouse epitrochleoanconeus muscle.

J Anat 2021 Jun 13. Epub 2021 Jun 13.

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.

Analysis of rodent muscles affords an opportunity to glean key insights into neuromuscular development and the detrimental impact of disease-causing genetic mutations. Muscles of the distal leg, for instance the gastrocnemius and tibialis anterior, are commonly used in such studies with mice and rats. However, thin and flat muscles, which can be dissected, processed and imaged without major disruption to muscle fibres and nerve-muscle contacts, are more suitable for accurate and detailed analyses of the peripheral motor nervous system. Read More

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Measuring the iron content of dopaminergic neurons in substantia nigra with MRI relaxometry.

Neuroimage 2021 Jun 10:118255. Epub 2021 Jun 10.

Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, Leipzig 04103, Germany; Center for Cognitive Neuroscience Berlin, Free University Berlin, Habelschwerdter Allee 45, Berlin, 14195, Germany.

In Parkinson's disease, the depletion of iron-rich dopaminergic neurons in nigrosome 1 of the substantia nigra precedes motor symptoms by two decades. Methods capable of monitoring this neuronal depletion, at an early disease stage, are needed for early diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is particularly suitable for this task due to its sensitivity to tissue microstructure and in particular, to iron. Read More

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Cortical hyperexcitability: Diagnostic and pathogenic biomarker of ALS.

Neurosci Lett 2021 Jun 10;759:136039. Epub 2021 Jun 10.

Brain and Mind Centre, University of Sydney and Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia.

Cortical hyperexcitability is an early and intrinsic feature of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS).. Importantly, cortical hyperexcitability appears to be associated with motor neuron degeneration, possibly via an anterograde glutamate-mediated excitotoxic process, thereby forming a pathogenic basis for ALS. Read More

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Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression.

J Cachexia Sarcopenia Muscle 2021 Jun 11. Epub 2021 Jun 11.

Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD, USA.

Background: Spinal muscular atrophy is an inherited neurodegenerative disease caused by insufficient levels of the survival motor neuron (SMN) protein. Recently approved treatments aimed at increasing SMN protein levels have dramatically improved patient survival and have altered the disease landscape. While restoring SMN levels slows motor neuron loss, many patients continue to have smaller muscles and do not achieve normal motor milestones. Read More

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Insight Into Spinocerebellar Ataxia Type 31 (SCA31) From Model.

Front Neurosci 2021 25;15:648133. Epub 2021 May 25.

Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Bunkyo City, Japan.

Spinocerebellar ataxia type 31 (SCA31) is a progressive neurodegenerative disease characterized by degeneration of Purkinje cells in the cerebellum. Its genetic cause is a 2.5- to 3. Read More

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NMJ-Analyser identifies subtle early changes in mouse models of neuromuscular disease.

Sci Rep 2021 Jun 10;11(1):12251. Epub 2021 Jun 10.

MRC Unit for Lifelong Health and Ageing, Department of Population Science and Experimental Medicine, University College London, London, WC1E 6BT, UK.

The neuromuscular junction (NMJ) is the peripheral synapse formed between a motor neuron axon terminal and a muscle fibre. NMJs are thought to be the primary site of peripheral pathology in many neuromuscular diseases, but innervation/denervation status is often assessed qualitatively with poor systematic criteria across studies, and separately from 3D morphological structure. Here, we describe the development of 'NMJ-Analyser', to comprehensively screen the morphology of NMJs and their corresponding innervation status automatically. Read More

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Involvement of ferroptosis in human motor neuron cell death.

Biochem Biophys Res Commun 2021 Jun 7;566:24-29. Epub 2021 Jun 7.

Department of Physiology, Keio University School of Medicine, Tokyo, 160-8582, Japan; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan. Electronic address:

Ferroptosis was recently defined as a novel type of programmed cell death depending on iron and lipid peroxidation. It is biologically different from other types of cell death such as apoptosis. While the involvement of ferroptosis in cancer, patient and animal model have been intensely studied, ferroptosis in human motor neuron model is still clearly unknown. Read More

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Familial clustering of primary lateral sclerosis and amyotrophic lateral sclerosis: Supplementary evidence for a continuum.

Eur J Neurol 2021 Jun 10. Epub 2021 Jun 10.

Faculty of Medicine, Instituto de Fisiologia, Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal.

Background And Purpose: Primary lateral sclerosis (PLS) is a motor neuron disorder characterized by a pure upper motor neuron degeneration in the bulbar and spinal regions. The key difference with amyotrophic lateral sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, the pathophysiology of PLS remains unknown, and the link with ALS still balances between a continuum and a separate entity from ALS. Read More

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